Chemical Carcinogenesis: Nature's Metabolic Mistake

Abstract

The normal biochemical defense against toxic chemicals, such as polyaromatic hydrocarbons, is to attach functional groups, such as hydroxyl, glucuronic acid, glutathione, etc. that tend to make the chemicals more water-soluble and readily excretable as harmless derivatives. However, chemical carcinogens form highly reactive intermediates on the path to final detoxification. These chemically unstable compounds, once formed, can readily attack cellular macromolecules, such as DNA, RNA, and protein, and alkylation of genetic material by these substances is critically involved with malignant transformation and mutagenesis.