title: Modulation of microsome-mediated aflatoxin B1 binding to exogenous and endogenous DNA by cytosolic glutathione S-transferases in rat and hamster livers.
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.
mesh_terms: D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002417:Cattle; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013950:Thymus Gland
chemical_list: D000348:Aflatoxins; D002273:Carcinogens; D004247:DNA; D016604:Aflatoxin B1; D005982:Glutathione Transferase