Effect of glutathione levels on aflatoxin B1-DNA binding in livers and kidneys of male rats and hamsters pretreated with buthionine sulfoximine and dimethylmaleate.
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.
Gopalan-Kriczky
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
Hiruma
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Lotlikar
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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
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