Toxicity and Carcinogenicity of the Aromatic Hydrocarbons

The general population is exposed to the toxic effect of benzene in areas in which atmospheric and indoor air exhibit high polluting values due to the benzene in regions with aggravated traffic, around the petrol stations, and in places where cigarettes are smoked 1-5 . Smoking has been incriminated as a unique and most important source of exposure to benzene for smokers 6, 7 and it is responsible for 50 of benzene exposure in the general population 6,7 . Tobacco smoke in the gas phase,...

Reconstitution of DNA damage by Nucleotide Pool Sanitation

The most stable mutagenic damage due to DNA oxidation, 8-oxoG, can be coupled with the nucleotides, cytosine and adenine, resulting in the formation of GC TA transversions 48 . The harmful behaviour of 8-oxoG is faced by complicated systems, such as the GO system, which includes the MutT, MutY and MutM proteins 49, 50 . In human cells this system has additional levels of complexity containing the BER, MMR and NER processes. The first line of defense is the elimination of 8-oxodG from the pool...

Function of the Pores During Oxidative Stress

The opening of the pores during oxidative stress is reversible. The in vitro opening of the pores from H2O2 in the presence of Ca2+ is fully reversed when the oxidative status is removed 110 . Under conditions of oxidative stress, O-' produced by the respiratory chain presents a linear increase 111 , whereas H2O2 is formed by superoxide dismutase. The mitochondria lack catalase and for this reason, H2O2 is reduced by GSH (glutathione peroxidase). As a result, it appears that pore activation is...

Toxicity and Carcinogenicity of the Eterocyclic Organic Compounds

Furan is a cyclic dien-ether in liquid form with an etheric odour it is non soluble in water but soluble in alcohol, acetone, benzene and ether 1 . Furan enters the human organism through the respiratory pathway. It is present in tobacco smoke and exhaust gases and it is detected in the exhaled air of smokers and non-smokers. Smokers exhale 0.25-98 g h while non smokers exhale 0.33-28 g h. Furan is considered to be a carcinogen in humans. Its carcinogenicity has been described in the literature...

Oono

Fig. 1.3 Oxidative damage of tissue cells via xanthine oxidase mechanism Fig. 1.3 Oxidative damage of tissue cells via xanthine oxidase mechanism Both chemical forms of O2-' are important, since endogenous reactions in biological systems take place in either an aqueous or non-aqueous environment. The different chemistry renders an ability to either give or gain an electron, which is equivalent to the behavior of gaining or losing a proton, respectively this is important in the chain of events...

Role of the Mut Proteins in the DNA Repair Processes

The cell faces two different problems related to GO adducts. One problem is the miscoding of GO damage into chromosomal DNA and a second problem is the incorporation of 8-oxo-dGTP into the DNA. The mutation rate is minimized when cells have an increased number of lines of defense against GO damage. In the case of chromosomal damage due to the GO system, nuclear DNA normality depends on the MutT and MutY proteins in order to avoid GC TA transversion 59, 60 . The MutM protein eliminates GO damage...

Gst

Oxidised to 3,4-epoxybutane-1,2-diole 46 . Epoxybutene is inactivated by glutathione-S-transferase. The same processes that take place in the liver of mice may also induce the transformation of butadiene in the human liver and lung cell cytoplasm and microsomes. During the inactivation of epoxybutene, metabolites which are detected in the urine of people exposed to butadiene, are created 47, 48 , (as well as in the urine of mice, rats, hamsters and monkeys). Diepoxybutane metabolites are not...

Cyp2e1 Cyp2b6 Cyp2c8 Cyp1a2

Acyl-CoA Aminoacid N-acyl transferase Acyl-CoA synthase Fig. 10.2 Toluene metabolism to hippuric acid toluene 73,74 . In mice, a low concentration of brain phospholipids was found, following continuous exposure to toluene for 30 days 78 . Furthermore, a decrease in the number of the neurons at the hippocampus, after a six-month exposure to toluene at 1500 ppm, for 6 hours daily has been ascertained. It has not yet been clarified whether these changes are due to fragmentation or inhibition of...

Oxygen and Nitrogen Free Radicals

Oxygen The Molecule Which is Sovereign in Oxidative Reactions Oxygen is an essential life element. Not counting hydrocarbons, there is a greater diversity of molecules with oxygen than with carbon. Dioxygen or diatomic oxygen (O2) is a diradical in its ground state with low solubility in aqueous solutions, that reacts in a kinetically peculiar fashion in oxidation reactions, and forms toxic byproducts as it gets reduced. As a result, all life forms evolved ways to deal with these problems,...

Gtp

Nitric oxide (NO) in humans is produced by three isoforms of NO-synthase endothelial (eNOS), neuronic (nNOS) and inducible (iNOS). NO reacts with superoxide (O2-) and produces peroxynitrite (ONOO-), whereas with oxygen it produces NO2 and N2O3. The latter or metric oxide react with thiols (RSH) and produce D-nitrosothiols RSH + N2O3 RS-NO + NO2 (or NO + R-SH R-S-N O) (Fig. 1.7) 79 . NO plays two discrete roles in the human organism in low concentrations, produced from eNOS and nNOS, it...

Cssg

Fig. 6.4 Transportation of glutathione bisulfide to the extracellular matrix by MRP protein pumps. GSSG is the substrate of MRP proteins. Under conditions of oxidative stress the reduction of GSSG by glutathione reductase is problematic. This leads to the exodus of a great amount of GSSG from the cell 1. Packer L. Am. J. Clin. Nutr. 53 4 Suppl 1050S-1055S 1991 2. Packer L. Proc. Soc. Exp. Biol. Med. 200 271-276 1992 3. Kappus H., Diplock A.T. Free Radical Biol. Med. 13 55-74 1992 4. Rice-Evans...

Effect of Oxidative Stress on PKC Function

Phospholipid Ip3

During oxidative stress, the cysteines of different proteins are oxidised irreversibly and this is the first defense mechanism against oxidation. Reducing substances inactivate proteins of great importance by differentiating their regulatory thiols. Protein kinase C is the one and only protein that is activated by oxidation during endogenous oxidative stress. Protein kinase C constitutes a family of corresponding enzymic isoforms, which are related to cell proliferation, differentiation and...