Quantitative comparison of covalent aflatoxin-DNA adducts formed in rat and mouse livers and kidneys.
The covalent interactions between aflatoxin B1 (AFB1) and DNA were investigated in the inbred F344 rat and noninbred CD -1 Swiss mouse. A good correlation was found between the level of covalent modification of DNA, species sensitivity, and organ specificity, to the toxic effects of AFB1. The patterns of AFB1 acid hydrolysis products from DNA isolated from the livers and kidneys of both species were examined. The principal acid hydrolysis product in all cases was identified as 2,3-dihydro-3-hydroxy-(N7-guanyl)AFB1. Minor products consisted of adducts formed by the chemical transformation of the AFB1-N7-substituted guanine moiety forming putative formamidopyrimidine derivatives and the activation of AFB1 metabolites, which also modified the N-7 guanine atom. These last-mentioned products were present in greater amounts in resistant tissues. In vitro studies on the activation of AFB1 by microsomal fractions of mouse and rat livers found that mouse liver microsomes were rapidly inactivated.
D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013950:Thymus Gland / Q000378:metabolism
D000348:Aflatoxins; D004247:DNA