title: Effect of glutathione levels on aflatoxin B1-DNA binding in livers and kidneys of male rats and hamsters pretreated with buthionine sulfoximine and dimethylmaleate.
abstract: The effects of pretreatment of buthionine sulfoximine (BSO) alone or in combination with diethylmaleate (DEM) on glutathione (GSH) levels and aflatoxin B1 (AFB1)-DNA binding have been examined in livers and kidneys of young male Fischer rats and Syrian golden hamsters 2 h after an intraperitoneal injection of [3H]AFB1 (0.4 mg/kg body wt.). Animals were treated with BSO (4 mmol/kg body wt.) alone at 4 h and 2 h or with DEM (3 mmol/kg body wt.) at 4 h and BSO at 2 h before AFB1 injection. Hepatic AFB1-DNA binding was about 29.0 and 6.0 pmol/mg DNA in rats and hamsters, respectively. In rats, BSO increased AFB1-DNA binding by about 40% with a drop in GSH by 70%. Treatment with DEM-BSO increased AFB1-DNA binding by about 80% with a concomitant drop in GSH in both species. In hamsters, BSO increased AFB1-DNA binding by only 10% with a 50% drop in GSH. The kidneys of both species have lower GSH levels and AFB1-DNA binding than their respective liver tissues. The effect of BSO alone or in combination with DEM on both GSH levels and AFB1-DNA binding are comparable even though BSO alone is less effective in both species. The role of modulation of GSH levels on AFB1-DNA binding and hence biological effects of AFB1 in these two species is discussed.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
authors.forename: P
authors.initials: P
authors.lastname: Gopalan-Kriczky
authors.forename: S
authors.initials: S
authors.lastname: Hiruma
authors.forename: P D
authors.initials: PD
authors.lastname: Lotlikar
mesh_terms: D016604:Aflatoxin B1 / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001711:Biotransformation; D019328:Buthionine Sulfoximine; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D005978:Glutathione / Q000378:metabolism* / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008647:Mesocricetus; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D018736:DNA Adducts; D008298:Maleates; C072611:aflatoxin B1-DNA adduct; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004247:DNA; D016604:Aflatoxin B1; D005982:Glutathione Transferase; C014476:diethyl maleate; D005978:Glutathione