Abstract:
:Interrelationships among induction of cytochrome P-450 (CYP) 1A1/2, decrease in connexin 32 (Cx32), and liver tumor-promoting activity by beta-naphthoflavone (BNF) in the promotion stage were examined in a 2-stage liver carcinogenesis model. A total of 20 male Fischer 344 rats were initiated with a single intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DEN) or were given the saline vehicle alone. Starting 2 weeks later, they were fed a diet containing 2%, 1%, or 0% BNF for 6 weeks. All animals were subjected to a two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. Absolute and relative liver weights were significantly increased in the DEN+BNF groups as compared to the DEN-alone group. Diffuse hepatocellular hypertrophy with cytoplasmic eosinophilia, sometimes accompanied by development of adenoma-like hepatic foci, was observed in the BNF-treated rats. Remarkable induction of cytochrome CYP 1A1/2 and significant increase in CYP 2E1 were noted in the DEN+BNF groups, and positive immunohistochemical staining for both was observed diffusely. The areas of Cx32-positive spots per hepatocyte in the centrilobular areas of livers of the BNF-treated rats were significantly decreased, but no changes were observed in periportal areas. The numbers and areas of foci positive for glutathione S-transferase placental form were increased in the BNF-treated groups. These results suggest that BNF is a liver tumor promoter that, unlike phenobarbital, does not induce CYP 2B1/2 isozymes, and there seems to be no direct relationship between CYP 1A1/2 induction and Cx32 reduction in BNF hepatocarcinogenesis.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Shoda T,Mitsumori K,Onodera H,Toyoda K,Uneyama C,Takada K,Hirose Mdoi
10.1177/019262330002800406subject
Has Abstractpub_date
2000-07-01 00:00:00pages
540-7issue
4eissn
0192-6233issn
1533-1601journal_volume
28pub_type
杂志文章abstract::The nonnucleoside inhibitor (NNI) of HIV-1 reverse transcriptase, PHI-346 (N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea), is a dual-function spermicidal agent with potent anti-HIV activity against drug-sensitive as well as drug-resistant HIV-1 strains with genotypic and phenotypic NNI resistance. PHI-3...
journal_title:Toxicologic pathology
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abstract::The title of the 2016 Society of Toxicologic Pathology (STP) Symposium was the "Basis and Relevance of Variation in Toxicologic Responses." Many factors may contribute to variation in toxicologic responses and can confound results, complicate interpretation of data, interfere with reproducibility, and make extrapolati...
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journal_title:Toxicologic pathology
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abstract::The B6C3F1 strain of mice is prone to develop liver nodules as animals grow older. This spontaneous tumor development is enhanced by dietary lipotrope deficiency. The present studies were performed to evaluate the liver of the B6C3F1 mice in early periods of lipotrope deficiency and before the nodules appear. Mice wer...
journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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