Mechanistic insights from biomarker studies: somatic mutations and rodent/human comparisons following exposure to a potential carcinogen.
The field of cancer molecular epidemiology is maturing rapidly. There is a vast armamentarium of biomarkers that is now used to assess human exposures to environmental carcinogens, the non-cancer effects of the exposures, and individual susceptibilities. There is also widespread realization that biomarkers must be validated before they are useful for human studies. One of the objectives of molecular epidemiology is the development of mechanistic insights into the carcinogenic process. Somatic mutations are biomarkers of effect that are proving useful in this regard. Mutations in reporter genes can serve as predisease mechanistic probes. A recent transitional epidemiological study of workers exposed to 1,3-butadiene evaluated a continuum of biomarkers of exposure, effect, and susceptibility. Results showed that relative concentrations of metabolites of this agent in humans are quite different from those in mice, which is the sensitive species for 1,3-butadiene carcinogenicity. Interspecies comparisons of the continuum of biological responses in mice, rats, and humans illustrate how these non-cancer endpoints might ultimately be used for making judgments as to cancer risk in humans.
Albertini
Richard J
RJ
Genetic Toxicology Laboratory, University of Vermont, Burlington 05401, USA. ralberti@zoo.uvm.edu
D000818:Animals; D015415:Biomarkers; D002070:Butadienes / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D051379:Mice; D009154:Mutation; D016273:Occupational Exposure; D051381:Rats; D013045:Species Specificity
D015415:Biomarkers; D002070:Butadienes; D002273:Carcinogens; D007041:Hypoxanthine Phosphoribosyltransferase; C031763:1,3-butadiene