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

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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.

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