A REVIEW OF THE DOSE-RESPONSE INDUCTION OF DNA ADDUCTS BY AFLATOXIN-B1 AND ITS IMPLICATIONS TO QUANTITATIVE CANCER-RISK ASSESSMENT

The induction of DNA adducts by aflatoxin B1 in the liver has been extensively reviewed in a quantitative cancer-risk assessment of aflatoxins (CDHS, 1990). Rat is the most sensitive species for aflatoxin tumorigenesis and liver is the most sensitive site. In vitro DNA-adduct studies were mostly on adduct identification and specificity of binding. In vivo studies provided dose-response relationship of aflatoxin B1, binding to DNA and DNA-adduct formation. Most in vivo studies were conducted in rats. The dose-response curves of DNA-adduct induction after ingestion or injection treatments in this species were reviewed. A linear dose-response relationship was observed in both injection and ingestion studies at low doses. For cancer-risk assessment, this observation is consistent with the assumption of the linear dose-response risk-assessment model for genotoxic agents, and justifies the use of this model for quantitative cancer-risk assessment for aflatoxins.