Modulation of microsome-mediated aflatoxin B1 binding to exogenous and endogenous DNA by cytosolic glutathione S-transferases in rat and hamster livers

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Abstract
Microsome mediated aflatoxin B1 (AFB1) binding to exogenous and endogenous DNA and its modulation by cytosolic glutathione (GSH) S-transferases have been examined in rat and hamster livers. Kinetic studies over a wide range of cytosol concentrations indicate that cytosol from the hamster is several-fold more effective than that from the rat in inhibiting AFB1 binding to exogenous calf thymus DNA mediated by microsomes from either species. Low concentrations of GSH (0.1–0.2 mM) are required for 50% inhibition of AFB1—DNA binding by cytosol. With exogenous DNA, combined microsome-cytosol fractions from the hamster give more AFB1—DNA binding than those from the rat. However, with nuclei as a source of endogenous DNA, AFB1—DNA binding is less with combined microsome-cytosol fractions from the hamster than those from the rat. Cytosolic inhibition of AFB1—DNA binding is almost completely reversed in the presence of 1 mM levels of either trichloropropene oxide or styrene oxide. Quantitation of AFB1—DNA binding and AFB1 -GSH conjugation indicate an inverse relationship between these two processes. Cytosol from the rat has less capacity than that from the hamster to form an AFB1—GSH conjugate. Hepatic GSH levels are about equal (6–7 mM) in both species. I.p. administration of [14C]AFB1 2 h before sacrifice gives more AFB1 binding to hepatic nuclear DNA in rats than in hamsters. However, depletion of hepatic GSH levels by 80% by i.p. administration of diethylmaleate (600 mg/kg) increases AFB1—DNA binding 2- to 3-fold in both species. The role of cytosolic GSH S-transferases in modulating hepatic AFB1—DNA binding in rats and hamsters is discussed.