Electromagnetic Radiation and Human Health

EMF Health Summit

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Ionizing Radiations And Ultraviolet Radiation

Low dosages (5 Gy or higher) of ionizing radiation exposure are known to induce adhesion molecules expression (Hareyama et al., 1998 Heckmann et al., 1998). Reactive oxygen species have been suggested to be involved in upregulating the expression of adhesion molecules following ionizing radiation (Baeuml et al., 1997). Both in vivo and in vitro studies have shown that UV radiation is able to modulate cell adhesion molecule expression and function (Grether-Beck et al., 1996 Hallahan and Viruda-chalam, 1997 Krutmann and Grewe, 1995 Krutmann and Trefzer, 1992 Norris, 1993). A UVA radiation-mediated increase in ICAM-1 expression in keratinocytes has been observed to be inhibited by singlet oxygen quenchers (Grether-Beck et al., 1996). Furthermore, it has been shown that the effect of UVA on ICAM-1 expression could be mimicked in

Ionizing Radiation

Ionizing radiation is well known to kill cells via the induction of DNA damage. In animals, certain cell types are much more sensitive than others, and this difference in sensitivity is taken advantage of for radiation therapy of malignancies. For example, rapidly dividing cells are known to be sensitive. One of the most successful uses of radiation therapy is for the treatment of B-cell leukemia, followed by bone marrow transplantation. Studies have shown that ionizing radiation induces cellular tyrosine phosphorylation in leukemic B-cell precursors, leading to the induction of programmed cell death. Treatment with tyrosine kinase inhibitors such as genistein and herbi-mycin A inhibited the induction of cellular tyrosine phosphorylation and prevented cell death in multiple leukemic B-cell precursor cell lines (Uckun et al., 1992), demonstrating that the activation of tyrosine phosphorylation signal pathways plays an important role in radiation-induced death in these cells. In...

Evaluation of Seizures and Epilepsy

Techniques are now available to directly correlate MRI abnormalities with EEG activity. Positron emission tomography (PET) images the brain's regional utilization of glucose, with asymmetries in glucose utilization, suggesting interictal or ictal areas of abnormality (7). Single photon emission computed tomography (SPECT) compares local blood flow discrepancies, a type of finding that is most informative when recorded during an actual seizure. Another promising new technique is magnetoencephalography (MEG), which assesses the brain's dynamic electromagnetic fields and can localize abnormally functioning areas (8). Finally, a wide array of metabolic aberrations can lead to seizures and epilepsy, with the specific evaluation depending on the patient's clinical presentation (9).

Sonochemistry as a Means to Accelerate Synthesis 31 General

Ultrasound can be described as alternating pressure waves (frequency higher than ca. 16 kHz) that in contrast to electromagnetic waves need an elastic medium to propagate. Sonochemistry in a liquid is a result of an acoustic cavitation occurring when ultrasound travels through the media with a concomitant formation of gas or vapour bubbles. The formation, expansion, and implosive collapse of such bubbles create local hot spots with temperatures estimated to reach several thousand Kelvins.38 The cavita-tion phenomenon is believed to be responsible for the various chemical and mechanical effects seen in sonochemical applications. The chemical outcome of ultrasonic irradiation is influenced by a number of factors including the choice of solvent, bulk

Apparent Diffusion Coefficient MRI

ADC-MRI offers some key advantages as a potential imaging biomarker of tumor treatment response. ADC-MRI does not require the injection of exogenous contrast agents, since it relies on the endogenous contrast mechanism of water diffusion. In addition, as an MRI- based method it does not involve exposure to ionizing radiation. Moreover, the ADC is an absolute biophysical quantity which, in principle, should be comparable across MRI hardware platforms. However, varying acquisition methodologies currently lead to some variability across hardware platforms and between different imaging centers, which could be addressed through better standardization of acquisition and processing protocols.

Nuclear Magnetic Resonance Spectrometry

Nuclear magnetic resonance (NMR) spectrometry is based on the fact that nuclei such as 1H, 13C, 19F, 31P possess a permanent nuclear magnetic moment. When placed in an external magnetic field (main field), they take certain well-defined orientations with respect to the direction of this field which correspond to distinct energy levels. For a given field value, transitions between neighbouring energy levels take place due to absorption of electromagnetic radiation of characteristic wavelengths at radio frequencies. The determination of these frequencies may be made either by sequential search of the resonance conditions (continuous-wave spectrometry) or by simultaneous excitation of all transitions with a multifrequency pulse followed by computer analysis of the free-induction decay of the irradiation emitted as the system returns to the initial state (pulsed spectrometry).

Infrared Spectroscopy 2101 Nitrous Oxide Infrared Spectra

The infrared region of the electromagnetic spectrum includes radiation at wavelengths between 0.7 and 500 im, or, in wavenumbers (the number of waves in a length of 1 cm), between 14,000 and 20 cm1. Infrared radiation is absorbed by the bending, stretching, and more complex motions of various functional groups in molecules. The large number of vibrations occurring simultaneously in even a simple molecule results in a complex absorption spectrum, which is characteristic of the functional groups present. The low energy of the absorbed photons in the infrared region is ideal for the detection of low-energy interactions, predicted to be of importance for anesthetic binding to macromolecules.

Tumor Suppressor Genes

> Whereas loss of RB1 function directly impinges on cell proliferation and differentiation, loss of tumor suppressor genes such as TP53 promotes tumor formation in a different fashion. Inactivation of TP53 compromises the ability of a cell to react to genomic damage, e.g. by ionizing radiation, as well as to hyperproliferation induced by oncogenes, or to viral infection. Therefore, loss of TP53 function permits survival and proliferation of cells accumulating mutations and thereby the emergence of a cancer. Several other tumor suppressors, e.g. BRCA1 and BRCA2, which are defective in familial breast cancers, also act primarily by protecting against genomic instability. Such 'caretakers' can be considered as a different class of tumor suppressors from 'gatekeepers' like RB1.

Redox Biology and Life

Many internal processes, influenced by lifestyle choices, can affect radical levels. Cigarette smoking and excessive consumption of alcohol result in measurably increased levels of radicals. Exogenous sources and environmental conditions can create radicals from ionizing radiation (sun exposure, cosmic rays, medical X-rays, or industrial processes), environmental toxins, and atmospheric pollution (ozone or nitric oxide produced from motor exhaust) as well. Biological systems have evolved to control or sequester these radicals and still other systems have evolved to repair cell damage once it occurs. But before we can explore them further, some additional definitions are necessary.

Oxidation of DNA bases

Attack of hydroxyl radicals to purine or pyrimidine bases produces other DNA damages. The structures of the degradation products arising from this reaction have been established mainly from studies with ionizing radiation,9 but many of them were similarly isolated from patients receiving anthracyclines for the treatment of breast cancer.10

Tp53 As A Different Kind Of Tumor Suppressor

Through these various functions TP53 coordinates the cellular response towards many kinds of damage to the genome, in particular, DNA double-strand breaks induced by chemical mutagens and ionizing radiation, as well as to certain kinds of cellular stress, such as guanine nucleotide imbalance, viral infection, and oncogene-induced hyperproliferation (Figure 5.6). TP53 is also involved in the regulation of replicative senescence ( 7.4). Different pathways signal various types of damage and stress to TP53 leading to a variety of post-translational modifications (Figure 5.7). Double-strand breaks induced by ionizing radiation activate ATM and or DNA-dependent protein kinase and extensive UV damage activates ATR ( 3.3) which phosphorylate TP53 at Ser15 and Ser37. The checkpoint protein kinases CHK1 and CHK2, which respond to DNA damage and specifically to mitotic disturbances phosphorylate Ser20. Phosphorylation at Ser15 and Ser 20 in particular block the interaction of TP53 with MDM2 HDM2...

Radiation Biology And Cancer

The biological effect of radiation on living cells tends to vary and depends on dose. It is well known that radiation is known to cause cancer, but in clinical practice, radiotherapy is an accepted form of cancer treatment. Injured or damaged cells may self-repair, die, or be involved in a misrepair process (see discussion later). High-radiation doses tend to kill cells, while low doses tend to damage or alter the genetic code (DNA) of irradiated cells. High-radiation doses can kill so many cells that tissues and organs are damaged immediately and tend to initiate a rapid body response, often called acute radiation syndrome. High-radiation dose manifests itself early. This was evident in many of the atomic bomb survivors in 1945 and in the emergency workers who responded to the 1986 Chernobyl nuclear power plant accident (Sali et al., 1996). Low doses of radiation over long periods may not cause immediate problems in body organs, but effects may occur at the cellular level. Genetic...

Quantitative Binding Affinity Measurement

The development of improved methods to accurately determine the absolute binding affinities of drug-like small molecules to their receptors is an active and fruitful area of research. Most methods for absolute affinity quantitation (as compared to relative affinity measurements based on displacement of a known inhibitor) rely on titration of a receptor by a ligand and readout of a signal corresponding to formation of the receptor-ligand complex. In the case of spectroscopic methods, the readout is based on emission or absorption of electromagnetic radiation for thermophysical methods such as isothermal calorimetry, the readout is based on emission of heat. In ALIS, the protein-ligand complex concentration is determined from the MS signal measured for the ligand after its dissociation from the complex. This section describes a straightforward ALIS-based titration method to quantify the binding affinities between unlabelled small molecules and their native protein targets.

Magnetic Resonance Imaging and Computed Tomography

Changes in vascular permeability and in extracellular, extravascular, and vascular volumes, and changes in blood flow can be measured by these techniques. MRI has the advantage over CT that it does not involve ionizing radiation, and that MRI contrast agents generally have a better toxicity profile than iodine contrast agents. In T1-weighted DCE-MRI, an intravenous bolus of gadolinium contrast agent enters tumor arterioles, passes through the capillary bed, and then drains via tumor veins. The signal enhancement is dependent on physiological and physical factors, including tissue perfusion, capillary surface area and permeability, and the volume

Cell Signaling and the Peroxiredoxin Based System Regulation of Transcription Factors Cell Cycle and Apoptosis

The activity of NF-kB is regulated at multiple levels by the Prdx-based system via the modulation of H2O2 concentrations, depending on tissue and subcellular distribution. Prdx 4 induces NF-kB via induction of the phosphorylation and thus degradation of IkB-a 68 . Trx translocates from the cytoplasm to the nucleus in response to oxidative stress, such as TNF-a or UV exposure 162 . Nuclear translocation of Trx also increases following exposure to ionizing radiation 163 or phorbol ester treatment 100 . By forming a complex with the DNA-binding loop of p50, nuclear Trx 1 then enhances the DNA-binding activity of NF-kB 97,162 . In contrast, cytoplasmic Trx 1 inhibits NF-kB activity by inhibiting IkB degradation 162 . Similar to Trx 1, nuclear Prdx 1 also augments the activity of the NF-kB 32 , while cytoplasmic Prdx 1 inhibits nuclear translocation of the transcription factor 32 . At the same time, Prdx 1 is itself regulated by NF-kB a new kB site in the Prdx 1 promoter was recently...

Induction Of Apoptosis By Reactive Oxygen Species

Signals generated by T-cell receptor cross-linking, phorbol 12-myristate-13-acetate + Ca2+ ionophore, glucocorticoids, or ionizing radiation all stimulate apoptotic cell death in thymocytes by signals that are initially distinct from each other. However, when these stimuli were administered to thymocyte cultures that were maintained under an atmosphere containing less than 20 ppm oxygen as opposed to one that contained 18.5 molecular oxygen, cell death was inhibited or abrogated, suggesting that the induction of death by all three different stimuli depends on the presence of molecular oxygen. N-Acetyl-L-cysteine inhibited the induction of death, suggesting a possible involvement of ROS in causing death (McLaughlin et al., 1996).

Magnetic Resonance Imaging

MRI is widely used clinically to assess tumor growth and for response evaluation. Anatomical information can be co-registered with functional and molecular information within a single imaging method. A further advantage compared to radiotracer techniques is that MRI does not use ionizing radiation and generally is more widely available than PET. MRI also offers good depth penetration and its resolution is usually higher than that of clinical PET scanners, although this depends on the exact protocol applied. A major disadvantage of MRI compared to radiotracer techniques is its lower sensitivity for the detection of targeted agents. Therefore, targeted molecular imaging agents for MRI have not entered clinical trials yet, except for the fibrin-specific contrast agent EP2140R 32 . The first MRI approach for molecular imaging of angiogenesis was the imaging of avP3 expression. By using Gd3+-containing paramagnetic liposomes and the avP3 specific antibody LM609 as a ligand, MRI of squamous...

Exogenous Hydrogen Peroxide as an Experimental Tool

In experimental cell culture systems, high levels of H2O2 cause changes in proteins that are probably physiological. For example, Prdx enzymes are inactivated by hyperoxidation (or overoxidation) of the peroxidatic cysteine (see also Chapter 6). This is apparent within minutes after applying high micromolar concentrations of H2O2 (100 mM) or butyl hydroperoxide (75 mM) to cell cultures 8, 63, 64 . Hyperoxidation has also been reported in vivo after treatment with ionizing radiation 65 or with paraquat 63 , which are both factors that induce ROS formation. Importantly, hyperoxidation has also been demonstrated in response to peroxides generated endogenously in response to a biological effector molecule such as glucose oxidase and tumor necrosis factor a (TNF-a) 8 .

Dietary Supplementation For Ocular Health

Because the eye is unique in its demand for oxygen required to sustain its high rate of metabolism (214), and because whenever functioning its tissues are concurrently exposed to the stress of electromagnetic radiation, it should not be surprising that the retina is exquisitely sensitive to homeostatic balance, influenced by the state of systemic health (292). It had been suspected by physicians for some time and epidemiologists more recently that nutrition, and in particular certain essential nutrients, might retard progression of age-related disease, and in particular, age-related eye disease (293-295). However, it was not until a large trial AREDS (Age-Related Eye Disease Study) trial of extended duration was undertaken by the National Eye Institute (NEI), initiated about 1992 and extending beyond seven years, that there was clinical evidence for benefit of dietary modification through supplementation. The AREDS trial demonstrated unambiguous benefit of supplementation with five...

Hypoxic selective agents

It is well established that hypoxic cells exist in solid tumors and that these cells are resistant to the cytotoxic effects of ionizing radiation.92,93 The non-cycling status of many hypoxic cells94 and the difficulty of achieving adequate drug concentrations in regions distant from blood vessels95 indicate that hypoxic cells may also be resistant to conventional chemotherapeutic agents. Therefore, there is a great interest in the design of drugs that are selectively cytotoxic under hypoxic conditions.96,97 The basic approach is to utilize net one-electron bio-reduction at a transition intermediate as the activation step. The properties of the Co(II) Co(III) redox couple offer distinct advantages in this quest.

Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging (fMRI) is a method for measuring hemodynamic (brain blood flow oxy-genation) responses related to neural activity in the brain. This technique has been used in conjunction with neuro-cognitive tasks to measure brain activation during discrete cognitive processes and effects of pharmacological agents on such processes. It is a recently developed form of neuroimaging. The advantages of fMRI include its low invasiveness, lack of radiation exposure, and relatively wide availability.

Damage Oxidation and Degradation

It has been known for some years that PS II is sensitive to electromagnetic radiation of both visible and ultraviolet wavelengths, particularly UVB 58 . The molecular basis of this sensitivity is under investigation and has revealed several different mechanisms for the deleterious effects of illumination. Loss of activity is often accompanied by poly-peptide cleavage, but it is not clear whether the reaction center is designed to promote controlled peptide cleavage or whether such cleavage is simply the gross observable result of extensive polypeptide damage. Until the covalent modifications accompanying activity loss are carefully characterized, it will not be possible to fully understand the mechanisms underlying inhibition.

Molecular Biology Of

Chronic myeloid leukemia (also chronic myelogeneous leukemia, commonly abbreviated CML) is a moderately frequent leukemia occurring in adults, most often in their 40's or 50's. While its causes are in general unknown, it has been observed following exposure to high doses of ionizing radiation.

[38 Redox Control of Cell Cycle Coupled Topolsomerase Ila Gene Expression

Mammalian topoisomerase Ila (Topo II) is a multifunctional protein involved in many cellular processes including replication, repair, transcription, recombination, chromosome condensation and segregation, and the G2 cell cycle checkpoint pathway.13 Topo II gene expression during the cell cycle is regulated mainly via posttranscriptional mechanisms of changes in mRNA stability.4 Topo II mRNA and protein levels increase in late S phase, peak in G2 M, and rapidly decrease after cell division.4 Several cancer therapeutic agents including ionizing radiation are known to generate reactive oxygen species and affect Topo II gene expression.5-8 Because a growing body of literature suggests the importance of oxygen radicals as possible physiological regulators of cell proliferation and expression of Topo II is proliferation dependent, development of methods to assay redox regulation of Topo II gene expression may provide a mechanistic understanding of how the

Electromagnetic Measures Of Brain Activity

The electromagnetic techniques record the scalp distribution of the field produced by the sum of mainly postsynaptic potentials of the neurons, each of which can be conceptualized as an electric dipole. EEG detects the electrical potential of the field, and MEG detects the magnetic component. The two techniques have very different technical requirements. EEG uses relatively simple equipment, basically a multielectrode helmet, an amplifying and filtering device, and a computer (Ebner et al. 1999). MEG, by contrast, employs cutting-edge technology (Ioannides 2006), because the detection of a magnetic field intensity as weak as the one produced by the brain ( 20,000 billion times weaker than the intensity of the Earth's magnetic field) requires the use of superconducting coil units based on superconducting quantum interference device (SQUID) technology. These units need to be specially cooled to a temperature near absolute zero. To avoid the intrusion of electromagnetic interference from...

Vitamin E As An Antioxidant

Vitamin E is liposoluble and as such is mostly present in cell membranes and in low-density lipoproteins (LDL). Free radicals are created both in metabolic processes and as a result of environment pollution (e.g., superoxide, hydroxyl radicals, nitrogen dioxide, ozone, heavy metals, halogenated hydrocarbons, ionizing radiation, and cigarette smoke).

Ray Powder Diffraction

X-rays are part of the electromagnetic spectrum lying between ultraviolet and gamma rays, and they are expressed in angstrom units (A). Diffraction is a scattered phenomena, and when X-rays are incident on crystalline solids, they are scattered in all directions. Scattering occurs as a result of the radiation wavelength being in the same order of magnitude as the interatomic distances within the crystal structure. X-rays are extensively used to characterize a crystal. In Figure 8, the relationship between the interplanar spacing and the angle of an incident beam is described by Bragg's equation.

Properties Relevant to Nuclear Medicine

The first report of nuclear isomerism by element-43 was by Segre and Seaborg in 1938.6 That isotope, 99mTc (t1 2 6.02 h, Eg 141 keV), possesses ideal properties for medical radioimaging because the 7 emission is sufficiently energetic to allow for visualization of sites deep within the human body by scintillation cameras without exposing patients to high levels of ionizing radiation. The daughter of 99mTc, the long-lived emitter 99Tc (Emax 293.6 keV), also does not contribute significantly to the overall radiation dose. A further attraction to 99mTc is the half-life of 6 h, which provides sufficient time for labeling, administration and biodistribution without having to use excessive amounts of radioactivity to compensate for losses due to radioactive decay. The long half-life also provides the opportunity to perform protracted imaging studies, which can take up to several hours, without having to significantly increase the injected dose.

The Development of Photodynamic Therapy

Photodynamic therapy was first investigated at the start of the twentieth century and the story of its discovery is an interesting example of scientific enquiry 5 . Oscar Raab, a student of Professor Hermann von Tappeiner at the Ludwig-Maximilian's University in Munich, had been conducting experiments on the toxic effects of acridine on paramecia (single cell organisms). He was surprised to find that in one experiment paramecia survived for 1.5 hours while in another experiment under identical conditions the paramecia survived for 15 hours. Raab, intrigued by his results, went back to his lab books and noted that there had been a heavy thunderstorm on the day of the second experiment, making the laboratory darker than normal. This led him to consider whether light had had an effect on the toxicity of the dye. His research group subsequently went on to discover that both light and oxygen were necessary components of this effect and coined the term photodynamic. Raab and his colleagues...

DNA repair system inhibitors

DNA is repeatedly exposed in normal cells to exogenous (e.g., UV light, ionizing radiation) and endogenous toxins (produced as a consequence of natural metabolic processes). It is estimated that the average rate of damage is about 104 events per cell per day. Therefore, DNA repair systems are vital to preserve the integrity of the genome, but their protective effect can be a disadvantage in cancer cells by reducing the cytotoxicity of antitumor agents, which is a cause of resistance.

Brain Disease Therapeutic Strategies And Brachial plexopathy BP

Radiation-induced BP (RBP) appears to be the most commonly reported syndrome of peripheral nerve injury caused by therapeutic irradiation. The disorder typically begins with hand and arm numbness and paresthesias followed by proximal weakness, and examination reveals sensory loss, reflex changes, weakness and atrophy in the distribution of the upper trunk, i.e. roots C5 and C6.14 Ipsilateral limb lymphedema and cutaneous radiation changes may be present, but Horner's syndrome is rare and pain is not a dominant complaint. Onset is usually insidious but the course is unpredictable. Although preserved functional ability is seen in about 50 of the patients,15,16 and there are occasional descriptions of spontaneous improvement, particularly of sensory symptoms,17 many patients become severely disabled after a slowly progressive course over several years,18 rarely with acute deterioration of motor functions.19 Involvement of the upper as opposed to the lower trunk is considered by some to...

Metabolic activation of carcinogens in the course of prostaglandin synthesis

Both the initiation of tumorigenesis as well as the progression from the benign to the malignant state are thought to be due to genotoxic events which lead to activation of proto-oncogenes and inactivation of tumor suppressor genes. These mutations are predominantly caused by environmental factors, i.e. chemicals, UV and ionizing radiation and tumor viruses. The great majority of chemical carcinogens have to be metabolically activated to become mutagenic. A major role in this 'toxification' is played by cytochrome P-450 monooxygenases which catalyze epoxidation and hy-droxylation of xenobiotics 36 , However, the oxygenation of environmental chemicals to genotoxic 'ultimate carcinogens' can also occur in the course of other metabolic processes. The most thoroughly studied pathway in this respect is prostaglandin biosynthesis. In particular, the peroxidase activity of prostaglandin H synthase (PGHS) is responsible for carcinogen activation, whereas COX activity is highly specific for...

Chemosensitizers Targeting Dnarepair Systems

The DNA-repair machinery of cells is activated triggering distinct repair pathways in response to different types of DNA damage. However, certain DNA-repair inhibitors capable of modulating DNA repair have the potential to act as anti-carcinogenic compounds by promoting cell death, rather than repair of potentially carcinogenic DNA damage mediated by error-prone DNA-repair pro-cesses.59 The discovery of changes in the DNA-repair pathways produced in various chemoresistant and radioresistant phenotypes, and their understanding, has identified the disruption of this process as a novel strategy to overcome intrinsic and or acquired resistance, especially to ionizing radiation and DNA-damaging agents. 3. and 4. Homology recombination (HR) and non-homologous end-joining (NHEJ) pathways repair double-strand breaks (DSBs) produced after use of ionizing radiation or administration of drugs that generate reactive oxygen species (ROS), alkylating agents, and topoisomerase inhibitors.

Formation of Tandem Lesions

The concept of the formation of clustered oxidative damage to DNA was proposed more than 15 years ago as a specific contribution of ionizing radiation 147 . Thus, interaction of high-energy photons (E > 100 keV) with nuclear DNA is expected to generate along the radiation track several ionization and excitation events as the result of energy deposition. This gives rise within cellular DNA to multiply damaged lesions 147 , which except for double strand breaks have not yet been characterized. It was suggested that they consist of several base lesions, abasic sites, and or strand breaks

The Comet Assay Singlecell Gel Electrophoresis

Classes from 0 (no detectable tail) to 4 (large tail, minimal head), giving an overall damage score of 0-400 or by computer image analysis, which gives the mean percentage of DNA in the tail. The scoring methods are equally reliable (Collins et al., 1997a), and with each, results can be expressed in terms of actual DNA break frequency by use of a calibration curve established with ionizing radiation to introduce known numbers of DNA breaks (Collins et al., 1996).

Total Internal Reflection Fluorescence Microscopy Tirfm Exploits Evanescent Wave Phenomena

For incident angles at or above 0c, the energy of the beam propagates as an evanescent wave into the aqueous medium for a short distance ( 300 nm), generating an electromagnetic field in the liquid with the same frequency as the incident light and with an intensity that decays exponentially

Sterilization Methods

Five sterilization processes are described in the USP steam, dry heat, filtration, gas, and ionizing radiation. All are commonly used for parenteral products, except gas and ionizing radiation, which are widely used for devices and surgical materials. To assist in the selection of the sterilization method, certain basic information and data must be gathered. This includes determining (i) the nature and amount of product bioburden and (ii) whether the product and container-closure system will have a predominantly moist or dry environment during sterilization. Both these factors are of critical importance in determining the conditions (time and temperature) of any sterilization method chosen.

Radioactive Heavy Metals

The widespread production and use of radioactive heavy metals for nuclear generation of electricity, nuclear weapons, laboratory research, manufacturing, and medical diagnosis have generated unique problems in dealing with accidental poisoning by such metals. Because the toxicity of radioactive metals is almost entirely a consequence of ionizing radiation, the therapeutic objective following exposure is chelation of the metals and their removal from the body as rapidly and completely as possible. Treatment of the acute radiation syndrome is largely symptomatic. Attempts have been made to investigate the effectiveness of organic reducing agents, such as mercaptamine (cysteamine), administered to prevent the formation of free radicals success has been limited.

Enymatic Measurement of Oxidative Base Damage to DNA in Single Cells

An alternative approach to the chromatographic measurements of oxidative base damage is represented by the modified versions of the alkaline single cell gel electro-phoresis or ''comet assay'' 262 , the alkaline elution technique 263 , and the alkaline unwinding method 264 . The comet assay, like the other methods, is applicable to isolated cells. This is a highly sensitive fluorescence-based detection method that allows, for example, the assessment of radiation-induced damage within human blood cells upon exposure to doses of ionizing radiation as low as 0.1 Gy 265 . However, the three assays in their basic version suffer from a lack of specificity in the measurement of the lesions they provide. Thus, the potential damage that may be monitored is very broad, consisting of single and double frank strand breaks, true and oxidized abasic sites, together with alkali-labile lesions. It should be also pointed out that transient strand breaks that may occur during DNA repair processes are...

Oxidative Base Damage in Cellular DNA

The association of bacterial DNA repair enzymes including the formamidopyr-imidine DNA glycosylase (Fpg) and the endonuclease III (endo III) proteins with the single cell gel electrophoretic assay has allowed the measurement of three main classes of radiation-induced damage in the DNA of human monocytes at a dose as low as 2 Gy 230 . In a recent study attempts were made to calibrate the modified comet assay by singling out the main nucleobase decomposition products that correspond to the Fpg-sensitive sites in cellular DNA exposed to relatively high doses of either gamma rays or UVA radiation 230,261,268 . This was achieved by HPLC-ECD for the measurement of 8-oxodGuo (35), whereas the search for FapyAde (54) and FapyGua (36) was made by HPLC-GC MS. Interestingly, it was found that 8-oxodGuo (35) and FapyGua (36) (relative ratio 29 71) were generated in a linear relationship with the applied doses of ionizing radiation within the dose ranges 30-80 and 250-1000 Gy, respectively. It may...

Levi J Beverly and Anthony J Capobianco

Aberrant Notch signaling contributes to more than half of all human T-cell leukemias, and accumulating evidence indicates Notch involvement in other human neoplasms. We developed a tetracycline inducible mouse model (Top-Notchic) to examine the genetic interactions underlying the development of Notch-induced neoplastic disease. Using this model we demonstrate that Notch suppresses p53 in lymphomagenesis through repression of the ARF-mdm2-p53 tumor surveillance network. Attenuation of Notch expression resulted in a dramatic increase in p53 levels that led to tumor regression by an apoptotic program However, all tumors relapsed with rapid kinetics. Furthermore, by directly inhibiting the mdm2-p53 interaction by using either ionizing radiation or the novel small molecule therapeutic Nutlin, p53 can be activated and cause tumor cell death, even in the presence of sustained Notch activity. Therefore, it is the suppression of p53 that provides the Achilles heel for Notch induced tumors, as...

HDACs and DNA Damage Repair Genome Integrity

SIRT1 is the leading HDAC involved in the regulation of DNA repair proteins through deacetylation, suggesting that it plays significant roles in DNA repair and genome integrity. As mentioned before, Ku70 and p53, the two important effectors downstream of the repair signal cascades initiated by double strand break (DSB) damage, are directly deacetylated and inhibited by SIRT1. SIRT1 also deacetylates many other DDR proteins. NBS1 is the regulatory subunit of MRE11-RAD50-NBS1 (MRN), a conserved nuclease complex that exhibits properties of a DNA damage sensor and is critical for the cellular response to DNA DSBs. Phosphorylation of NBS1 by the ATM kinase is essential for its activation in response to DNA damage (Buscemi et al. 2001). Our previous work demonstrated that NBS1 is an acetylated protein and that its acetylation level is tightly regulated by SIRT1. SIRT1 associates with the MRN complex and keeps NBS1 in a hypoacetylated state, which is required for the ionizing...

Antithyroid Drugs And Other Thyroid Inhibitors

A large number of compounds interfere either directly or indirectly with the synthesis, release, or action of thyroid hormones (Table 56-2). Inhibitors are classified into four categories (1) antithyroid drugs, which interfere directly with the synthesis of thyroid hormones (2) ionic inhibitors, which block the iodide transport mechanism (3) high concentrations of iodine itself, which decrease release of thyroid hormones and may also decrease hormone synthesis and (4) radioactive iodine, which damages the gland with ionizing radiation. Adjuvant therapy with drugs that have no specific effects on thyroid hormone synthesis is useful in controlling the peripheral manifestations of thyrotoxicosis, including inhibitors of the peripheral deiodination of T4 to T3, 3 adrenergic receptor antagonists, and Ca2+ channel blockers.

Regulatory Disulfides Controlling Transcription Factor Activity in the Bacterial and Yeast Responses to Oxidative Stress

Oxidative stress has been defined as a disturbance in the prooxidant-antioxidant balance in favor of prooxidants.40 Thus oxidative stress can result from increased levels of reactive oxygen species such as superoxide anion (02* ), hydrogen peroxide (H202), hydroxyl radical (HO*) and alkyl hydroperoxides (ROOH). Reactive oxygen species are byproducts of normal metabolic processes but elevated levels of these prooxidants can be generated by environmental factors such as ionizing radiation, heavy metals or other redox-active chemicals such as the 02* generating compound menadione. If allowed to accumulate unchecked these molecules exceed the normal antioxidant buffering capacity of the cell leading to indiscriminate damage to cellular components including DNA, proteins and lipids. Cells also may experience oxidative stress resulting from a drop in the thiol disulfide ratio within the cytosol or within an organelle. This drop in the thiol disulfide ratio can occur under certain growth...

Secondary Oxidation of 8Oxo78Dihydroguanine Components

There is a growing body of evidence showing that 8-oxodGuo (35), whose oxidation potential is about 0.5 eV lower than that of dGuo (28) 121 , is a preferential target for numerous one-electron oxidizing agents. These include Na2IrCl6 128,129 , K3Fe(CN)6, CoCl2 KHSO5 130 , high-valent chromium complex 131 , peroxyl radicals 132 , triplet ketones, oxyl radicals 124 , ionizing radiation through the direct effect 133 , and riboflavin as a type I photosensitizer 134 . Interestingly, the two (R*)-and (S*)-diastereomers of (Sp) nucleosides (38) were found to be the predominant

Biological Effects of Radiation

The absorption of ionizing radiation by living cells always produces effects potentially harmful to the irradiated organism. An undesirable aspect to the medical use of radiation is that a small number of the atoms in the body tissues will have electrons removed as a result of the photons. Radiation that does this is called ionizing radiation and is potentially damaging to body tissues. Therefore, in using ionizing radiation, as in using other pharmaceutical agents, the risks must be balanced with the medical benefits provided for the patient. per gram of any tissue. The unit of exposure for x-rays and y radiation in air, the roentgen, is used to specify radiation levels in the environment. One roentgen is the amount of radiation that produces 1 electrostatic unit (ESU) of charge of either sign per 0.001293 g of air at standard temperature and pressure (STP). The SI has adopted the gray (Gy) to replace the rad (1 Gy 100 rads). Again, the more traditional unit is still used in clinical...

Radioactive Assay Technologies

All SPAs are based upon the phenomenon of scintillation. Scintillation is an energy transfer that results from the interactions of particles of ionizing radiation and the de-localized electrons found in conjugated aromatic hydrocarbons or in inorganic crystals. When the decay particle collides with

Dna Intercalation And Its Consequences

Many anticancer drugs in clinical use (e.g. anthracyclines, mitoxantrone, dactinomy-cin) interact with DNA through intercalation, which can be defined as the process by which compounds containing planar aromatic or heteroaromatic ring systems are inserted between adjacent base pairs perpendicularly to the axis of the helix and without disturbing the overall stacking pattern due to Watson-Crick hydrogen bonding. Since many typical intercalating agents contain three or four fused rings that absorb light in the UV-visible region of the electromagnetic spectrum, they are usually known as chromophores. Besides the chromophore, other substitu-ents in the intercalator molecule may highly influence the binding mechanism, the geometry of the ligand-DNA complex, and the sequence selectivity, if any.

Split and recombine strategy

Split And Pool Combinatorial Chemistry

Glass-encased microchips that are pretuned to emit a unique binary code when pulsed with electromagnetic radiation 15 are widely used to tag and identify laboratory animals via subcutaneous injection. An unlimited number of unique identifier tags are available based on the size of the transponder binary codes. Association of an encodable transponder with a synthesis site during a split and recombine synthesis could allow the storage of relevant background information such as reaction path, chemical inputs or chemical transformation. Hence, uploading these data from the microchip at any time during the experiment would provide detailed information about the identity of the chemical structure associated with each synthesis site.

Manufacturing Techniques

Aqueous suspensions are prepared in much the same manner, except that before bringing the batch to final volume with additional sterile water, the solid that is to be suspended is previously rendered sterile by heat, by exposure to ethylene oxide, or ionizing radiation (y or electrons), or by dissolution in an appropriate solvent, sterile filtration, and aseptic crystallization. The sterile solid is then added to the batch, either directly or by first dispersing the solid in a small portion of the batch. After adequate dispersion, the batch is brought to final volume with sterile water (329). Because the eye is sensitive to particles larger than 25 im in diameter, proper raw material specifications for particle size of any dispersed solids must be established and verified on each lot of raw material and final product. The control of particle size of the final suspended material is very important, not only for comfort of the product but also for improving physical stability and...

Key Advantages of Imaging Biomarkers

Finally, there are inherent limitations in imaging biomarkers that are not likely to be fully mitigated by future development. Within the spectrum of potential imaging biomarkers, those that rely on endogenous contrast mechanisms have the advantage of avoiding the added complexity and safety concerns introduced by the use of exogenous imaging agents. However, such image-based functional measures are often inherently nonspecific, relying on biological models in which the connection between measurement and function may not be interpreted easily or directly. In addition, there is a growing perception that the increased use of nuclear and CT modalities, which utilize ionizing radiation, presents a public health concern 62,63 . Diagnostic imaging has been guided by the principle that the risks of ionizing radiation should always be weighed against the benefits of the imaging procedure to the patient 64 i however, in some cases, radiation doses from medical tests may exceed limits known to...

Cell Protection Mechanisms In Cancer

A similar argument can be made for ionizing radiation. The effects of ionizing radiation on normal cells are mitigated by cellular protection mechanisms, in addition to DNA repair. For instance, polyamines stabilize cellular macromolecules such as DNA and structural RNAs. Tocopherol, ascorbate, carotenoids, and glutathione can all act to quench the effect of hydroxyl radicals and other reactive oxygen species. Therefore, it may in some cases be helpful to deplete such compounds prior to therapy.

Anatomical And Physiological Considerations Of The Gastrointestinal Tract

Villi Diagram Black And White

The surface epithelial cells of the small intestine are renewed rapidly and regularly. It takes about two days for the cells of the duodenum to be renewed completely. As a result of its rapid renewal rate, the intestinal epithelium is susceptible to various factors that may influence proliferation. Exposure of the intestine to ionizing radiation and cytotoxic drugs (such as folic acid antagonists and colchicine) reduce the cell renewal rate.

Base Excision Repair DNA Glycosylases

Endonuclease Viii

Inside the cell, DNA is subject to attack by a wide variety of reactive species, including electrophilic oxidants, ionizing radiation, ultraviolet light, methylating agents, and even water (13). Nearly all the resulting adducts interfere with the normal template function of the genome in one way or another, and many give rise to mutations by inducing illegitimate recombination or miscoding during DNA replication (14). All free-standing organisms dedicate a considerable fraction of their genomes to encoding proteins that search for and repair DNA

IKKgModification Triggers NFkB Activation in Response to DNA Damage

Atm Kinase Interactions

Topoisomerase inhibitors etoposide (Eto) or camptothecin (Cpt) exhibit cyto-static effects by inducing DNA double-strand breaks and therefore are potent inducers of NF-kB activity (Fig. 4). The actual sensor of DNA double-stranded breaks is unknown. The primary cellular transducer for DNA damage is the ATM (ataxia telangiectasia mutated) kinase. ATM-deficient cells from patients with the genomic instability ataxia telangiectasia are blocked in NF-kB activation in response genotoxic stress agents, such as y-ionizing radiation (IR) or Cpt (Li et al. 2001 Piret et al. 1999). Upon Eto or Cpt treatment, IKKy enters the nucleus where it associates with PIDD (p53-induced death domain) and RIP1, both proteins having essential functions in the control of NF-kB activation in response to DNA damage (Hur et al. 2003 Janssens and Tschopp 2006). Further, IKKy is retained in the nucleus by site-directed sumoylation mediated by PIASy (protein inhibitor of activated STATy) that acts as the SUMO (small...

Ultraviolet Visible Infrared Atomic Absorption Fluorescence Turbidimetry Nephelometry And Raman Measurement

Absorption spectrophotometry is the measurement of an interaction between electromagnetic radiation and the molecules, or atoms, of a chemical substance. Techniques frequently employed in pharmaceutical analysis include UV, visible, IR, and atomic absorption spectroscopy. Spectrophotometry measurement in the visible region was formerly referred to as colorimetry however, it is more precise to use the term colorimetry only when considering human perception of color. Fluorescence spectrophotometry is the measurement of the emission of light from a chemical substance while it is being exposed to UV, visible, or other electromagnetic radiation. In general, the light emitted by a fluorescent solution is of maximum intensity at a wavelength longer than that of the exciting radiation, usually by some 20 to 30 nm.

ATM Regulates ATR Chromatin Loading in Response to DNA Double Strand Breaks

DNA double-strand breaks (DSBs) are among the most deleterious lesions that can challenge genomic integrity. Concomitant to the repair of the breaks, a rapid signaling cascade must be coordinated at the lesion site that leads to the activation of cell cycle checkpoints and or apoptosis. In this context, ataxia telangiectasia mutated (ATM) and ATM and Rad-3-related (ATR) protein kinases are the earliest signaling molecules that are known to initiate the transduction cascade at damage sites. The current model places ATM and ATR in separate molecular routes that orchestrate distinct pathways of the checkpoint responses. Whereas ATM signals DSBs arising from ionizing radiation (IR) through a Chk2-dependent pathway, ATR is activated in a variety of replication-linked DSBs and leads to activation of the checkpoints in a Chk1 kinase-dependent manner. However, activation of the G2 M checkpoint in response to IR escapes this accepted paradigm because it is dependent on both ATM and ATR but...

Reconstitution of Double Strand Breaks by Homologous Recombination HR and Nonhomologous End Joining NHEJ

The reconstitution of DSB in mammalian cells is accomplished by homologous and non-homologous mechanisms. These mechanisms are however, inefficient in correcting different diseases 69, 70 . According to the literature, NHEJ happens more frequently as compared to HR. However, the reconstitution mechanism depends on the condition of the cell cycle. Recent research has shown that HR is the prevailing mechanism in the completion of the S-phase of the cell cycle, provided that there is the same copy of the DNA helix (sister chromatid) available. In the G1 phase of the cell cycle, NHEJ is the preferable mechanism for the reconstitution of the cell cycle 71,72 . Exactly the same copy of the DNA helix, the sister chromatid, is mostly preferred (twice out of three times) in the homologous or heterologous chromosome 73 . Even if HR is exempted from a mistake, NHEJ may lose or win some nucleotides. HR and NHEJ are different mechanisms which demand completely different...

Series Introduction

Normal metabolism is dependent upon oxgyen, a free radical. Through evolution, oxygen was chosen as the terminal electron acceptor for respiration. The two unpaired electrons of oxygen spin in the same direction thus, oxygen is a biradical, but is not a very dangerous free radical. Other oxygen-derived free radical species, such as superoxide or hydroxyl radicals, formed during metabolism or by ionizing radiation are stronger oxidants and are therefore more dangerous.

Summary

Tumor hypoxia, or the condition of low oxygen, is a key factor for tumor progression and treatment resistance. Because hypoxic tumor cells are more resistant to ionizing radiation, hypoxia has been a focus of clinical research in radiation therapy for half a century. During this period, interest in targeting tumor hypoxia has waxed and waned as promising treatments emerged from the laboratory, only to fail in the clinics. With the development of new radiation targeting strategies, specifically intensity-modulated radiotherapy (IMRT) and image guidance technologies (image-guided RT IGRT), there is a strong interest in imaging hypoxia for radiation targeting and dose escalation. In this review, we will discuss the role of hypoxia imaging, specifically positron emission tomography (PET)-based imaging with hypoxia-specific tracers, for directing radiation treatment in solid tumors.

General Risk Factors

Increased risk has been observed for a variety of occupations in studies of occupational factors and prostate cancer 13,16,47,48 . There is no evidence for an association of cadmium exposure or exposures in the rubber industry and prostate cancer risk (see 13,49,50 ). There is weak to inconclusive evidence for a positive association between farming and prostate cancer risk 13,16,47,48, 51 . Workers in the nuclear industry and armed services personnel may be at increased risk for prostate cancer 13,17,48,52 . However the evidence for exposure to ionizing radiation as a risk factor is equivocal 13,17,48,52-54 .

Imaging

Ultrasonography avoids effects associated with ionizing radiation and also provides real-time assessment of soft tissue structures. Nerves and blood vessels within soft tissue structures, muscles, tendons, and many internal organs can be assessed with ultrasound techniques. Ultrasound, however, does not provide the resolution capacity with CT or MRI for imaging soft tissue structure, nor does ultrasound penetrate through bone well or provide a good assessment of anatomically deep structures like the spinal cord.

Infection

Morpholinos have been used to pretarget radioisotopes to tumors as an experimental diagnostic or therapeutic technique. Targeting radioisotopes to tumors by bonding the radioisotopes directly to antibodies suffers from disadvantages conferred by the large size of the antibodies - the large macro-molecules diffuse slowly into tumors and clear slowly from the blood, so delivery of a therapeutically useful dose of radiation into the tumor using radiolabelled antibodies requires exposing healthy tissues to potentially damaging doses of radioactivity. Radiation dose to non-tumor tissues can be decreased by pretargeting. A pretargeting scheme developed by Donald Hnatowich's group involves treatment with an antibody bound to a Morpholino, allowing time for the large molecules to bind in the tumor and clear from the blood. This is then followed by treatment with a complementary Morpholino bound to a radioisotope. The relative small Morpholino-isotope conjugate enters tumors relatively rapidly...

Chapter Overview

Diagnostic medical imaging encompasses a group of techniques often used in the diagnosis and subsequent treatment of disease. Medical imaging procedures are typically considered low-risk events in comparison to direct surgical visualization and often provide information or treatment methods that are simply not available by any other means. Medical imaging techniques use electromagnetic radiation to pass through tissue and convey the internal information necessary to create an image of the tissue or organ. The different types of medical imaging techniques diverge in their physical means, methods, and the information that they can provide. All of the techniques can provide anatomical and or functional information that is often displayed as an image for interpretation by a physician trained to evaluate the meaning of the image in the context of the disease state. Medical imaging began with Roentgen's discovery of x-rays in 1895, and it has been the domain of diagnostic radiology ever...

Radiosensitizers

Radiotherapy is one of the major approaches to cancer therapy, and can be defined as the medical use of ionizing radiation as part of cancer treatment. It is based on the generation of hydroxyl radicals from homolytic fragmentation of water molecules on local application of ionizing radiation. This fragmentation can be preceded by ionization of water molecules (Fig. 4.40A) or by their excitation (Fig. 4.40B). Damage by ionizing radiation is enhanced by the presence of oxygen by a factor of 2- to 3.5-fold and therefore oxygen can be considered to act as a radio-sensitizer. This so-called ''oxygen effect'' is due to the property of oxygen of reacting with biomolecule radicals to generate other radicals that cannot be

Imaging Modalities

Biomedical imaging measures the interactions of electromagnetic waves with the body or the emission of electromagnetic waves from the body. These imaging modalities utilize the physical characteristics of the waves across the electromagnetic spectrum. Covering the range from low-frequency to high-frequency electromagnetic waves, ultrasound imaging, MRI, optical imaging, X-ray radiography, and X-ray CT, g-scintigraphy, SPECT, and PET are routinely used for preclinical and clinical studies (Table 1).

Raman Spectroscopy

As a complementary tool to IR in vibrational spectroscopy, Raman spectroscopy is one of the fastest growing analytical techniques in use today due to its ability to reveal fundamental molecular structural information and immediate chemical environment through light-transparent materials and without sample preparation. It also offers submicron spatial resolution and very high sensitivity (when coupled with surface-enhanced Raman spectroscopy or SERS). IR spectroscopy is based on the absorption of electromagnetic radiation by a molecular system, whereas Raman spectroscopy relies upon inelastic scattering of the system. Strong IR bands are related to polar functional groups, whereas non-polar functional groups give rise to strong Raman bands. Raman is an extremely flexible technique and offers many advantages over IR spectroscopy including a wide variety of acceptable sample forms, flexible sample interfaces and sample size, no sample preparation, and high sampling rates. Furthermore,...

Injury

Obliterative endarteritis is a classical pathological feature of late radiation-induced normal tissue injury.14 The ischemia and hypoxia that accompany vascular atrophy are important causes of parenchymal atrophy and loss of tissue function.1516 Radiation fibrosis contributes to loss of function, and several models have been advanced to explain how this develops. A wound repair model describes chronic inflammation induced by chronic cell necrosis after radiation therapy as a potent source of fibrogenic cytokines and fibrogenesis, processes proposed to explain scarring in surgical wounds.17 A rather different explanation is offered by a model that postulates a direct interaction between ionizing radiation and stromal fibroblasts, the latter undergoing differentiation after in vitro exposure to ionizing radiation to a postmitotic senescent phenotype characterized by up-regulated production of collagen, an important component of fibrotic tissue.1819

And Alain Sarasin

Oxidative damage to cellular DNA arises from attack by free radicals produced by cellular metabolism or by exogenous agents such as UV-A and ionizing radiation. Among the numerous types of base damage produced, 8-oxoguanine (8-oxoG or GO) is one of the most abundant. Because 8-oxoG readily mispairs with A, it is highly mutagenic, inducing G-to-T transversions in the absence of efficient repair. The base pair GO C can be repaired in human cells by base excision repair (BER) initiated by the hOGGl gene product, a bifunctional DNA glycosylase with the dual function of lesion removal and incision of the DNA by AP (apurinic)-lyase activity.1

Antioxidants

Free radicals and their metabolites released by ionization of water mediate the classical cytotoxic effects of ionizing radiation via DNA strand breakage. The postulated antifibrotic effects of antioxidants prescribed years after exposure cannot be related to this phase of free-radical attack. Other spheres of free-radical effects are legion, in lipid membranes and aqueous environments, inside cells and outside. Although reactive oxygen species interact randomly with molecular targets, the effects are not merely stochastic in the sense that cell-signaling mediated by redox reactions have important roles in cellular homeostasis.63 The processes modulated by antioxidants are not likely to be specific to the repair of radiotherapy injuries, since the fibrotic response to ionizing

Test Preparation

Common solvents are suitable, and ordinary (nonfluorescing) glass specimen cells can be used. The IR region of the electromagnetic spectrum extends from 0.8 to 400 m. From 800 to 2500 nm (0.8 to 2.5 m) is generally considered to be the near-IR (NIR) region from 2.5 to 25 m (4000 to 400cm-1) is generally considered to be the mid-range (mid-IR) region and from 25 to 400 m is generally considered to be the far-IR (FIR) region. Unless otherwise specified in the individual monograph, the region from 3800 to 650 cm-1 (2.6 to 15 m) should be used to ascertain compliance with monograph specifications for IR absorption.

Outline of AMS

AMS was developed in the 1970s and has been applied to the fields of archeology, geology, and environmental and earth sciences. The measurement principle of AMS is based on the separation and direct measurement of 14C and 12C atoms without any disintegration time requirements. The AMS system is a highly sensitive analysis method that can be used for measuring radiocarbon concentration (14C 12C ratio). The sensitivity of AMS is more than 1000 times higher than that of conventional beta-ray counting methods such as the liquid scintillation counter. Because the required amount of radioactivity for AMS is far less than that required for a conventional test with 14C, AMS can be employed without any concerns about radiation exposure in volunteers in clinical trials. The American Research Group at the National Laboratory is a pioneer of AMS work within the biochemical community 7, 8 . This technology is now being applied in microdose studies for new drug development because 14C is stably...

Breast Cancer

> Carcinoma of the breast is a major lethal cancer in females in the Western world, on a par with lung and colon cancer. Most cases occur in postmenopausal women, but a significant number of younger women are afflicted, often in families with a hereditary predisposition. Known risk factors include the length of the life-time exposure to estrogens, ionizing radiation, cigarette smoking, and a high-fat diet.

Gary L Schieven

Oxidative stress has been shown to activate tyrosine phosphorylation signal transduction pathways in a wide variety of cell types. These pathways are normally under the control of ligand binding to receptors. Oxidative stress is able to bypass this normal receptor control to activate pathways that are often the central regulatory pathways for cellular proliferation and functional responses. Ionizing radiation, ultraviolet (UV) radiation, and chemical agents can activate these tyrosine phosphorylation pathways. In the case of exposure of B cells to ionizing radiation, activation of the pathways leads to the induction of programmed cell death. In other cases, activation of signal pathways may induce a pattern of gene expression that would be protective. Phosphotyrosine phosphatases (PTP) are highly sensitive to inhibition by oxidative stress, and inhibition of these enzymes leads to the accumulation of phosphotyrosine signaling. A second potential mechanism by which oxidative stress may...

Optical Rotation

Light is a form of electromagnetic radiation and is composed of electric and magnetic fields that oscillate in all directions perpendicular to each other and to the direction from which the beam is propagated. In plane-polarized light, the component electric and magnetic fields oscillate as in ordinary light, except that they are contained within two perpendicular planes. When the electrical part of the plane-polarized light interacts with an asymmetric molecule, the direction of the field is altered or rotated because of the dissymmetry of the molecule. The substance through which the light passes is said to be optically active.

Instillation [EU

Radiation Emission or propagation of electromagnetic energy (waves rays), or the waves rays themselves a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. NIH Radiotherapy The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. NIH

Photochemotherapy

Electromagnetic radiation is defined by its wavelength and frequency for convenience, it can be classified into different regions based on its photon energy. For therapeutic purposes, dermatologists are most concerned with the ultraviolet (UV) B (290 320 nm), A-I (320 340 nm), and A-II (340-400 nm) and visible (400-800 nm) spectrum. UVB is the most erythrogenic and melanogenic. It is the major action spectrum for sunburn, tanning, skin cancer, and photoaging. The longer wavelengths of UVA are a thousand times less erythrogenic than UVB however, they penetrate more deeply into the skin and contribute substantially to photoaging and photosensitiv-ity diseases. They also enhance UVB-induced erythema and increase the risk of skin carcinogen-esis. Visible radiation may augment the severity of some photosensitive eruptions. Electromagnetic radiation has proven to be highly efficacious in the treatment of numerous dermatologic diseases. Phototherapy and photochemotherapy are treatment...

Ag014699

Double strand breaks generated by ionizing radiation and ROS, or indirectly by DNA-damaging anticancer drugs such as alkylating agents and topoisomerase inhibitors, are repaired by either the HR or the NHEJ pathways. The enzymes involved in these pathways are members of the phosphatidylinositol 3-kinase (PI3K) superfamily and have become anticancer targets because their inhibition confers radio- or chemo-sensitization to tumor cells.85 These enzymes can be considered as molecular sensor of DSBs, and the most relevant targets in this area86 are LY-294002 is another non-selective, competitive inhibitor of PI-3 kinases. Although this compound significantly sensitizers ATM-proficient cells to ionizing radiation and DBS-inducing chemotherapeutics, such as etoposide, doxorubicin, and camptothecin, its relatively low stability, fast metabolic degradation, and in vivo toxicity have prevented its clinical evaluation in humans. However, LY-294002 has been used as a lead compound in the...

Strandbreak Repair

Wrn Gene And Cancer

Like mismatch repair during DNA replication, repair of DNA strand-breaks goes on rather 'quietly'. However, this changes dramatically, when DNA double-strand breaks are generated. These can arise by physiological and non-physiological mechanisms, endogenous processes and exogenous mutagens. During DNA replication, a double-strand break can result from a single-strand break, if this is not repaired, before it is encountered by the replisome. Sometimes two single-strand breaks may by chance occur closely together leading to a double-strand break. Other double-strand breaks are caused by exogenous agents. Some viruses encode enzymes that cut DNA in a similar fashion as restriction enzymes, e.g. retroviral integrases. Ionizing radiation can generate single- as well as double-strand DNA breaks as do several chemical carcinogens and some drugs used in chemotherapy. Bleomycin, e.g., cuts DNA directly, and topoisomerase inhibitors generate strand breaks by inhibition of these enzymes ( 22.2)....