Historical Overview of Chemical Carcinogenesis

There is increasing evidence that carcinogens play a major role in causation of human cancer. This chapter reviews the advances in carcinogenesis research from a historical perspective. The classes of carcinogens surveyed include polycyclic aromatic hydrocarbons, aromatic amines and amides, nitroarenes, heterocyclic amines formed in cooking, N-nitroso compounds, aflatoxins, natural oils such as safrole, and other natural products, such as the pyrrolizidine alkaloids. For each of these categories, information is presented on historical developments, environmental occurrence, the identities of the active metabolites, the pathways of enzymatic activation, and the structures of the adducts formed with DNA. Despite the chemical and structural diversity of the carcinogens, the evidence indicates that their mechanisms of tumorigenesis are fundamentally similar. The active metabolites of most carcinogens are electrophiles (or reactive oxygen species) that react with DNA to induce mutations and/or other genotoxic changes.