Interactions of Aflatoxin B1 and Alkylating Agents with DNA: Structural and Functional Studies
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Excerpt
DNA as a Cellular Target for Activated Chemical Carcinogens
Over the past two decades, an increasing body of epidemiological evidence has suggested a role for certain environmental chemicals in the etiologies of a number of human genetic diseases, including cancer (Doll and Peto 1981). The mechanistic details of the means by which chemicals induce cellular transformation are still, for the most part, incompletely understood, but there is good evidence that the chemically induced alteration of informational macromolecules is an early and probably requisite event. Indeed, most chemicals that are potent carcinogens bind very effectively to DNA, RNA, and protein in vivo, with metabolic activation often required to convert the carcinogens to reactive, usually electrophilic derivatives that form covalent adducts with these macromolecules (Miller 1978).
DNA is considered by most workers to be the critical macromolecular target for adduct formation by activated carcinogens. This conclusion is based in part on the...
