Chemical carcinogenesis: a current biological perspective.

The ultimate end-point of a cancer-inducing exposure to a carcinogen is the appearance of a localized collection of cells (i) undergoing inappropriate proliferation, (ii) expanding locally and invading the surrounding tissue and (iii) releasing cells that generate in turn new collections of proliferating cells in distant sites. Most cancers are made up of heterogeneous cell populations with considerable diversity in cell structure, in chromosomal and genetic makeup and in biochemical properties as well as in states of differentiation. Although the cell type and biological behaviour do vary with different carcinogens, there is no known relationship between the nature and metabolism of the carcinogen and the nature of the ultimate cancer. Even though a minority of chemical carcinogens induce highly predictable types of neoplasms, e.g., vinyl chloride, 1,2-dimethylhydrazine, /3-naphthylamine, etc., modification of the conditions of exposure can change the spectrum of cancers induced. To cite but one example: with 1,2-dimethylhydrazine and some other carcinogens, acute exposure, when coupled with surgical partial hepatectomy, may induce a high incidence of liver cell cancer while in the absence of the surgical intervention, few or no such neoplasms are seen. To date, major correlations exist only between the cell or tissue distribution of the metabolizing and/or repair enzymes and the tissue site of cancer development but not with the nature of the cancer.