Metabolism of chemical carcinogens.
The transformation of chemicals is important in carcinogenesis, both in bioactivation and detoxification. Major advances in the past 20 years include appreciation of the migration of reactive electrophiles, the ability of Phase II conjugating enzymes to activate chemicals, understanding of the human enzymes, the realization that DNA modification can result from endogenous chemicals, and the demonstration that cancers can result from the metabolism of chemicals to non-covalently bound products. Pathways of transformation in which major insight was gained during the past 20 years include nitropolycyclic hydrocarbons, polycyclic hydrocarbons and their diols, vinyl halides and dihaloalkanes. Advances in analytical methods and recombinant DNA technology contributed greatly to the study of metabolism of chemical carcinogens. Major advances have been made in the assignment of roles of individual enzymes in reactions. The knowledge developed in this field has contributed to growth in the areas of chemoprevention, molecular epidemiology and species comparisons of risk. Some of the areas in which future development relevant to carcinogen metabolism is expected involve pathways of transformation of certain chemicals, regulation of genes coding for many of the enzymes under consideration and genomics.
Guengerich
F P
FP
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638B Medical Research Building I, 23rd Avenue South at Pierce, Nashville, Tennessee 37232-146, USA. guengerich@toxicology.mc.vanderbilt.edu
D000818:Animals; D015415:Biomarkers; D001711:Biotransformation; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D017720:Molecular Epidemiology; D009369:Neoplasms / Q000209:etiology; D010084:Oxidation-Reduction
D015415:Biomarkers; D002273:Carcinogens; D004798:Enzymes