Carcinogen-DNA and protein adducts: biomarkers for cohort selection and modifiable endpoints in chemoprevention trials.
Chemical-specific markers have been developed for a number of environmental carcinogens for use as molecular dosimeters of individual exposure. In addition to contributing substantially to the specificity and sensitivity of epidemiological studies aimed at determining the role of environmental agents in the etiology of human cancers, some of these biomarkers may prove to be useful endpoints for assessing the efficacy of preventive interventions including exposure avoidance or remediation and chemoprevention. Biomarkers of the biologically effective dose may be particularly useful in this context in that they provide a mechanistic linkage between exposure and disease outcome. The biologically effective dose reflects the amount of toxicant that has interacted with its critical molecular target and can be measured through a variety of analytical techniques as either carcinogen-DNA or -protein adducts. Approaches for the development and validation of aflatoxin adduct biomarkers are presented as a paradigm for the application of carcinogen-specific markers for cohort selection and as modifiable endpoints for assessing efficacy in chemoprevention trials.
Kensler
T W
TW
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, 21205, USA.
Groopman
J D
JD
D016604:Aflatoxin B1 / Q000031:analogs & derivatives / Q000652:urine; D000348:Aflatoxins / Q000009:adverse effects; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002273:Carcinogens / Q000378:metabolism*; D002986:Clinical Trials as Topic / Q000379:methods; D015331:Cohort Studies; D018736:DNA Adducts / Q000032:analysis*; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D011719:Pyrazines / Q000627:therapeutic use; D012307:Risk Factors; D013871:Thiones; D013876:Thiophenes
D000348:Aflatoxins; D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D002273:Carcinogens; D018736:DNA Adducts; D011506:Proteins; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D006147:Guanine; C028319:2,3-dihydro-2-(N(7)-guanyl)-3-hydroxyaflatoxin B1; C026209:oltipraz; D016604:Aflatoxin B1