Chemical Toxicants and Carcinogenesis

Abstract

Cancer is due to a complex multistep process of sequential transformation of a normal cell into a proliferating cell, able to spread to other tissues by invasion or metastasis. Three steps charaterize this transformation: initiation, promotion and progression. Initiation is due to the interaction of an initiating agent, or its metabolite(s), with the nucleotides of DNA with the formation of adducts. These permutational lesions can give rise to mutations, essentially dunng translesion DNA synthesis. Cell proliferation caused by promotors increases the number of mutations. Several sequential mutations affecting, in the same cell, protooncogenes (which give rise to oncogenes), or tumor suppressor genes (which results in inactive tumor suppressor proteins) lead to cancer. These mutations occur mostly at hot-spots and are often characteristic of the chemical at the origin of the adducts.