Differential effects of acetaminophen pretreatment on hepatic aflatoxin B(1)-DNA binding, cellular proliferation, and aflatoxin B1-induced hepatic foci in rats and hamsters.
Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B1 (AFB(1))-DNA binding, cellular proliferation, and AFB(1)-induced glutathione S-transferase placental form (GST-P) positive hepatocytes and foci have been examined in young male rats and hamsters. Intraperitoneal (i.p.) dosing of 600mg AAP 3h before AFB(1) i.p. injection showed three-fold more AFB(1)-DNA binding in hamsters and 40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine incorporation was not significant (0.4-0.6%) 24-96h after AAP (600mg) treatment of rats; however, proliferation was stimulated and was maximum (11%) in hamsters at 72h after AAP treatment. Dosing of rats with AFB(1) alone at 0.5 or 2.5mg level gave an appreciable number of GST-P positive minifoci (two to nine cells) with a few foci larger than 100 microm; pretreatment with AAP (300 or 600mg) 48h before 0.5 or 2.5mg AFB(1) had no effect on the number and focal area of foci. In hamsters, 1 or 2mg AFB(1) alone yielded GST-P positive hepatocytes without any minifoci. Pretreatment with AAP (600mg) 48 or 72h before 1 or 2mg AFB(1) produced increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes are observed after AAP pretreatment in hamsters compared to rats.
Hiruma
S
S
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Gopalan-Kriczky
P
P
Qin
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G
Gaughan
J P
JP
Lotlikar
P D
PD
D000082:Acetaminophen / Q000494:pharmacology*; D016604:Aflatoxin B1 / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D004247:DNA; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D005978:Glutathione