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Chemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide

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dc.contributor.authorSurh, Young-Joon-
dc.contributor.authorKim, Seung Gon-
dc.contributor.authorPark, Kwang-Kyun-
dc.contributor.authorSohn, Yeowon-
dc.contributor.authorLee, Jong-Min-
dc.contributor.authorKim, Nak Doo-
dc.contributor.authorMiller, James A.-
dc.date.accessioned2021-01-31T10:25:31Z-
dc.date.available2021-01-31T10:25:31Z-
dc.date.issued1998-07-
dc.identifier.citationCarcinogenesis, Vol.19 No.7, pp.1263-1267-
dc.identifier.issn0143-3334-
dc.identifier.other5280-
dc.identifier.urihttps://hdl.handle.net/10371/172917-
dc.description.abstract2-(Allylthio)pyrazine (2-AP), synthesized for its possible use as a hepatoprotective agent, has been found to selectively inhibit rat hepatic cytochrome P450 2E1 (Kim et al,, Biochem, Pharmacol., 53, 261-269, 1997), while it enhances the activities of phase II detoxification enzymes such as glutathione S-transferase and epoxide hydrolase, As part of a program in evaluating the chemopreventive potential of 2-AP, we have determined its effects on hepatotoxicity, mutagenicity and tumorigenicity of vinyl carbamate (VC), a prototypic hepatocarcinogen preferentially activated by P450 2E1 to the ultimate carcinogenic metabolite vinyl carbamate epoxide (VCO), which undergoes detoxification by glutathione conjugation and oxirane hydrolysis. Administration of 2-AP (100 mg/kg body wt) to male Sprague-Dawley rats by gavage, 2 days, 1 day and 4 h prior to VC or VCO, markedly ameliorated the hepatotoxicity of these compounds as determined by decreased serum aspartate aminotransferase and alanine aminotransferase activities. Furthermore, 2-AP pre-treatment significantly suppressed the VC-induced hepatocarcinogenesis in infant male B6C3F(1) mice, In a separate experiment, the multiplicities of skin tumors formed in female ICR mice treated with 5.8 mu mol of VC or VCO were inhibited 58 and 70%, respectively, by pre-treatment with 2-AP by oral administration. The mutational spectrum of ras-oncogene in papillomas was not altered by 2-AP pre-treatment. 2-AP also inhibited the mutagenicity of VC in the Salmonella-microsome assay. Taken together, these findings suggest that 2-AP is a potential chemopreventive agent.-
dc.titleChemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide-
dc.typeArticle-
dc.contributor.AlternativeAuthor서영준-
dc.identifier.doi10.1093/carcin/19.7.1263-
dc.citation.journaltitleCarcinogenesis-
dc.identifier.scopusid2-s2.0-0031926582-
dc.citation.endpage1267-
dc.citation.number7-
dc.citation.startpage1263-
dc.citation.volume19-
dc.identifier.urlhttps://academic.oup.com/carcin/article/19/7/1263/2365516-
dc.identifier.rimsid5280-
dc.identifier.sci000074884300014-
dc.contributor.affiliatedAuthorSurh, Young-Joon-
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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