Aflatoxin B1-induced DNA adduct formation in murine kidney and liver

Abstract

Aflatoxicosis is a life-threatening nephrotoxic condition arising from eating foods highly contaminated with aflatoxin-producing molds. Additionally, chronic aflatoxin exposures are linked to enhanced hepatocellular carcinomas. Using recent advances in mass spectrometry for the detection of aflatoxin B₁ (AFB₁) DNA adducts, we present data which show generation of these adducts in the kidney, albeit at ≈ 100-fold lower levels than in the liver of the same animal. This result is consistent with tissue-specific differences in the expression of cytochrome P450s implicated in the activation of AFB₁. Although the mechanisms underlying aflatoxin-induced nephrotoxicity had been postulated to be driven by the generation of high levels of reactive oxygen species, measurement of oxidatively-induced DNA base damage did not reveal evidence for genotoxic induction of these lesions. Overall, this investigation provides evidence of the formation of aflatoxin-specific adducts in kidney tissue and challenges the hypothesis of acute aflatoxin exposures generating reactive oxygen-mediated DNA damage.