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Chemical carcinogenesis.

Weston A; Harris CC

Cancer medicine 5th edition. Bast RC, Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E, eds. Hamilton, Ontario, Canada: BC Decker, Inc., 2000 Jun; :185-194

20021091

Chemical carcinogenesis is a multi-stage process that begins with exposure, usually to complex mixtures of chemicals that are found in the human environment (Table 12.1). 1-3 Once internationalized, carcinogens frequently are subjected to competing metabolic pathways of activation and detoxication, although some reactive environmental chemicals can act directly. Variations among individuals in the metabolism of carcinogens, together with differences in DNA-repair capacity and response to tumor promoters, govern the relative risk of an individual. 4 The initial genetic change that occurs as the result of chemical-DNA interaction is termed tumor inhibition. Thus, initiated cells are irreversibly altered and are at greater risk of malignant conversion that are normal cells. The epigenetic effects of tumor promoters facilitate the clonal expansion of the initiated cell. 5 This selective, clonal growth advantage results in the formation of a focus of preneoplastic cells. These cells are more vulnerable to progress toward tumorigenesis because they present a larger, more rapidly proliferating target population for the further action of chemical carcinogens, oncogenic viruses, and other cofactors. Additional genetic changes occur, and consequently, the accumulation of mutations, which may activate protooncogenes and inactivate tumor-suppressor genes, leads to malignant conversion, tumor progression, and metastasis. The underlying genetic mechanisms that regulate chemical carcinogenesis are becoming increasingly well understood, and the insights generated have assisted in the development of methodologies designed to assess human cancer risk and susceptibility factors. The results of these latter studies are further intended to mold strategies for cancer prevention.

Carcinogenesis; Carcinogenicity; Carcinogens; Exposure assessment; Genetic factors; Genetics; Risk analysis; Risk factors; Tumorigens; Tumorigenesis; Tumors; Cancer; Occupational exposure; Exposure levels; Environmental factors; Tobacco smoke; Lung cancer; Bladder cancer

20000601

Chapter

Bast RC; Kufe DW; Pollock RE; Weichselbaum RR; Holland JF; Frei E

2000

9781550091137

HELD

Cancer medicine 5th edition

WV