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 B(1) (AFB(1))-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 [(3)H]AFB(1)-DNA adducts in the hepatocytes; however, the partitioning of AFB(1) into cellular compartments was not affected by carnitine. The attenuating effect of carnitine on AFB(1)-DNA adduct formation was also present in a cell-free system, but there was lack of specificity because acetylcarnitine and gamma-aminobutyric acid (GABA) were equally effective. Carnitine appears to interfere with bioactivation of AFB(1) and binding of AFB(1)-epoxide to DNA. On the contrary, carnitine enhanced the binding of AFB(1) and its epoxide to microsomal proteins, plasma proteins and bovine serum albumin. These results indicate that carnitine diverts AFB(1)-epoxide away from DNA by promoting binding to proteins. We conclude that modulation of AFB(1) binding to proteins and DNA by carnitine alters the carcinogenic and hepatotoxic potential of AFB(1) and poses concerns about the human AFB(1)-exposure data based on the AFB(1)-albumin adduct concentrations as a biomarker.
Yatim
A M
AM
Department of Nutrition, College of Human Ecology, University of Tennessee, Knoxville, TN 37996-1900, USA.
Sachan
D S
DS
D016604:Aflatoxin B1 / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002331:Carnitine / Q000494:pharmacology*; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D018736:DNA Adducts / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
D015415:Biomarkers; D018736:DNA Adducts; D016604:Aflatoxin B1; D002794:Choline; D002331:Carnitine; D005998:Glycine