Carnitine Alters Binding of Aflatoxin to DNA and Proteins in Rat Hepatocytes and Cell-Free Systems

The objective of this study was to determine effects of L-carnitine on aflatoxin B1 (AFB1)-DNA adduct formation in isolated rat hepatocytes, its dose response, specificity and mode of action. All experiments were conducted in either freshly isolated rat hepatocytes or cell-free systems. There was negative linear correlation between the dosage of carnitine and formation of [3H]AFB1-DNA adducts in the hepatocytes; however, the partitioning of AFB1 into cellular compartments was not affected by carnitine. The attenuating effect of carnitine on AFB1-DNA adduct formation was also present in a cell-free system, but there was lack of specificity because acetylcarnitine and γ-aminobutyric acid (GABA) were equally effective. Carnitine appears to interfere with bioactivation of AFB1 and binding of AFB1-epoxide to DNA. On the contrary, carnitine enhanced the binding of AFB1 and its epoxide to microsomal proteins, plasma proteins and bovine serum albumin. These results indicate that carnitine diverts AFB1-epoxide away from DNA by promoting binding to proteins. We conclude that modulation of AFB1 binding to proteins and DNA by carnitine alters the carcinogenic and hepatotoxic potential of AFB1 and poses concerns about the human AFB1-exposure data based on the AFB1-albumin adduct concentrations as a biomarker.