ABSTRACT
The development of neoplasms mediated by chemicals in both experimental animals and humans is a complex, multistep process, involving a series of genetic and epigenetic alterations. Ultimately, the outcome of exposure to a chemical carcinogen is a function of the internal or effective dose and duration of exposure to the chemical and cancer-modifying agents and intrinsic susceptibility of the exposed animal or human. Replicating cells are susceptible to neoplastic transformation by carcinogens and, because of that, factors that increase cell replication can enhance the response of a tissue to a carcinogen, while those that suppress replication can diminish susceptibility. Chemicals that are not themselves carcinogenic, but that enhance carcinogenicity are referred to as cocarcinogens. A wide variety of chemicals, both natural and synthetic, have carcinogenic activity in rodents. DNA-reactive carcinogens operate primarily in the first steps of oncogenesis by binding to the DNA of target cells to effect initiation and neoplastic transformation.
