INHIBITION OF COVALENT DNA-BINDING AND MUTAGENICITY OF BENZO[A]PYRENEBY -DITHIETANE-2-YLIDENE)-2-[N-(4-METHYLTHIAZOL-2-YL) CARBAMOYL]ACETATE (YH439), A NOVEL HEPATOPROTECTIVE AGENT

ne)-2[N-(4-methyl-2-thiazol-2-yl)carbamoyl]acetate (YH439) was synthes ized as a hepatoprotective drug for the treatment of chronic hepatitis and liver cirrhosis. In the present investigation, we have tested YH4 39 for its chemoprotective activity against the carcinogen benzo[n]pyr ene. The drug exhibited dose-dependent protection against bacterial mu tagenesis 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 o f benzo[a]pyrene, was also ameliorated by YH439 in a dose-dependent ma nner. The results of this study suggest that YH439 has a potential as a chemopreventive agent.