**4. Molecular biology and chemical carcinogenesis**

The discovery of DNA as the genetic material by Avery, MacLeod, and McCarthy (1944) and the description of the structure of DNA by Watson and Crick (1953) indicated that DNA was the cellular target for activated chemical carcinogens and that mutations (alterations in the sequence of bases making up amino acids) were key to understanding mechanisms of cancer. This led to defining the structure of the principal adducts in DNA (complexes of DNA and a carcinogen or its metabolite) by benzo (*a*) pyrene (Carrel et al., 1997) and aflatoxin B1 (Croy et al., 1978). The concepts developed in investigating mechanisms of chemical carcinogenesis also led to discoveries that are relevant to other human conditions in addition to cancer, including atherosclerosis, cirrhosis, and aging. The fact that genetic changes in individual cancer cells are essentially irreversible and that malignant changes are transmitted from one generation of cells to another strongly points to DNA as the critical cellular target modified by environmental chemicals. DNA damage by chemicals occurs randomly; the phenotypes of associated carcinogenic changes are determined by selection. Epidemiologic studies from all over the world have identified environmental and

occupational chemicals as potential carcinogens. The most definitive epidemiologic studies have been those in which a small group is exposed to a tremendously large amount of a specific chemical, such as aniline dyes. The table below (table 3) lists some of the fairly well characterized chemicals sites where they have induced cancer.


Table 3. List of Chemical Carcinogens.
