Modulation of aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci by pretreatment of rats with phenobarbital and buthionine sulfoximine.
Induction of glutathione S-transferase placental form (GST-P) positive hepatic foci has been examined by immunohistochemical analysis in young male Fischer rats 3 weeks after a single i.p. injection of aflatoxin B1 (AFB1). Pretreatment of rats with L-buthionine sulfoximine (BSO), a GSH depleter, at a dose of 4 mmol/kg body wt 4 and 2 h before 1.0 mg AFB1 treatment enhanced both the number of AFB1-induced hepatic foci and the area occupied by these foci by approximately 400 and 575% above their respective controls without affecting the mean diameter of these foci. Pretreatment of rats with 0.1% phenobarbital (PB) in their drinking water for 1 week before AFB1 (1 mg) treatment, inhibited AFB1-induced foci almost completely. However, the number of AFB1-induced foci in PB-pretreated rats was not significantly increased by BSO pretreatment.
Gopalan
P
P
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
Tsuji
K
K
Lehmann
K
K
Kimura
M
M
Shinozuka
H
H
Sato
K
K
Lotlikar
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PD
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D004247:DNA / Q000378:metabolism; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D000964:Antimetabolites, Antineoplastic; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004247:DNA; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D010634:Phenobarbital