Inhibitory effects of S-methylcysteine and cysteine on the promoting potential of sodium phenobarbital on rat liver carcinogenesis

The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of rodent hepatocarcinogenesis in a medium-term bioassay previously develop ed by Ito were examined. Initiation was induced by a single dose of diethyl nitrosamine (DEN), followed by dietary administration of the promoter sodiu m phenobarbital (NaPB) 2 weeks later, for 6 weeks. Partial hepatectomy was conducted on all the animals at week 3, Inhibitory potential was evaluated by analyzing two markers of carcinogenesis, namely numbers of glutathione S -transferase placental form (GST-P)-positive foci, and proliferating cell n uclear antigen (PCNA), In addition, the level of ornithine decarboxylase (O DC), one of the rate-limiting enzymes of polyamine metabolism induced by pr omoters, was analyzed. SMC and cysteine induced significant reduction in th e areas of GST-P-positive foci, A significant reduction in the PCNA index w as observed in the entire liver as well as in GST-P-positive areas. SMC als o induced down-regulation of the ODC enzyme activity, Thus, SMC and cystein e were found to inhibit the promotion stage of DEN-induced hepatocarcinogen esis. No cocarcinogenic effects were evident on administration of either of these chemicals with NaPB.