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) bindingto 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-GSHconjugation in vitro using rat and hamster liver subcellularfractions is elucidated in this report. Even though hamsterliver microsomes catalyzed AFB₁ binding to exogenous DNA threetimes as much as the rat, hamster cytosol inhibited AFB₁-DNAbinding catalyzed by either microsomes severalfold more thanthe rat cytosol. AFB₁ - DNA binding is found to be inverselyrelated to AFB₁-GSH conjugation at all AFB₁ concentrations (2–100µM)studied. Presence of either styrene oxide or 3,3,3-trichloropropeneoxide at 1 mM level diminished AFB₁-GSH formation in vitro confirmingsome competition by these epoxides with AFB₁-epoxide for cytosolicGSH S-transferases. In a reconstituted system with endogenousDNA, the ratio of AFB₁-GSH to AFB₁-DNA binding was found tobe 10–15 times higher with the hamster in comparison withthe rat indicating enhanced inactivation of the ultimate carcinogenicmetabolite in the hamster. These results are discussed in relationto AFB₁-DNA binding and AFB₁ hepatocardnogenicity in resistantand sensitive species.