Comparative kinetic studies on aflatoxin B1-DNA binding and aflatoxin B1-glutathione conjugation with rat and hamster livers in vitro.
Inhibition of microsome mediated aflatoxin B1 (AFB1) binding to exogenous or endogenous DNA by cytosolic glutathione (GSH) S-transferases is well established from our earlier studies. Correlation between inhibition of AFB1-DNA binding and AFB1-GSH conjugation in vitro using rat and hamster liver subcellular fractions is elucidated in this report. Even though hamster liver microsomes catalyzed AFB1 binding to exogenous DNA three times as much as the rat, hamster cytosol inhibited AFB1-DNA binding catalyzed by either microsomes severalfold more than the rat cytosol. AFB1-DNA binding is found to be inversely related to AFB1-GSH conjugation at all AFB1 concentrations (2-100 microM) studied. Presence of either styrene oxide or 3,3,3-trichloropropene oxide at 1 mM level diminished AFB1-GSH formation in vitro confirming some competition by these epoxides with AFB1-epoxide for cytosolic GSH S-transferases. In a reconstituted system with endogenous DNA, the ratio of AFB1-GSH to AFB1-DNA binding was found to be 10-15 times higher with the hamster in comparison with the rat indicating enhanced inactivation of the ultimate carcinogenic metabolite in the hamster. These results are discussed in relation to AFB1-DNA binding and AFB1 hepatocarcinogenicity in resistant and sensitive species.
D016604:Aflatoxin B1 / Q000031:analogs & derivatives; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011919:Rats, Inbred Strains
D000348:Aflatoxins; C006426:aflatoxin B1-2,3-oxide; D004247:DNA; D016604:Aflatoxin B1; D005978:Glutathione