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Inhibition of covalent DNA binding and mutagenicity of benzo[a]pyrene by isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2-yl) carbamoyl]acetate (YH439), a novel hepatoprotective agent
Cited 7 time in
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Cited 11 time in Scopus
- Authors
- Issue Date
- 1996-04
- Publisher
- Elsevier B.V.
- Citation
- Mutation Research - Genetic Toxicology, Vol.367 No.4, pp.219-224
- Abstract
- Isopropyl-2-(1,3-dithietane-2-ylidene)-2[N-(4-methyl-2-thiazol-2-yl)carbamoyl]acetate (YH439) was synthesized as a hepatoprotective drug for the treatment of chronic hepatitis and liver cirrhosis. In the present investigation, we have tested YH439 for its chemoprotective activity against the carcinogen benzo[n]pyrene. The drug exhibited dose-dependent protection against bacterial mutagenesis induced by benzo[n]pyrene and its covalent binding to DNA in vitro mediated by rat hepatic postmitochondrial supernatant enriched with NADPH. The direct mutagenicity of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, the ultimate electrophilic and carcinogenic metabolite of benzo[a]pyrene, was also ameliorated by YH439 in a dose-dependent manner. The results of this study suggest that YH439 has a potential as a chemopreventive agent.
- ISSN
- 0165-1218
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