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Ethyl Carbamate 2-Naphthylamina

2-Acatylaminofluor«na o N/N^

Ethyl Carbamate 2-Naphthylamina

2-Acatylaminofluor«na

Aflatoxin B1

Grisaofulvin

Figure 4-2. Structures of representative carcinogens.

Aflatoxin B1

Grisaofulvin

Figure 4-2. Structures of representative carcinogens.

In addition to alkylating agents used to treat cancer that are carcinogens themselves, other types of drugs have been shown to induce cancer in experimental animals. The antifungal antibiotic griseofulvin (a fungal product) has been shown to cause liver tumors in mice. Here, too, the presumed ultimate carcinogen is the 2',3'-epoxide compound (Fig. 4-2).

The chemically induced carcinogenic process is not fully understood. Cancer is obviously the end result of a series of complex events, each controlled by one or more exogenous and endogenous factors. Whether the carcinogen is primary and an electrophilic species, or must first be converted to one by hepatic metabolism enzymes, it is the elec-trophiles that are believed to react with specific cellular and molecular receptors, primarily, though not exclusively, with DNA. These interactions are influenced by various stereochemical conditions and competitive inhibitors that have not yet been elucidated. Much of the initial alterations (damage?) to DNA (and RNA) are subject to restoration by enzymatic repair mechanisms. The extent to which this repair fails may represent the formation of abnormal receptors that are now immune to the repair systems. Cells containing them might then represent the early, latent cancer cell. Further growth leads to a tumor. Finally, by an as yet unknown mechanism called progression the tumor transforms into an independent undifferentiated malignant neoplasm.

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