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 eysteine on the promotion stages of rodent hepatocar‐cinogenesis in a medium‐term bioassay previously developed by Ito were examined. Initiation was induced by a single dose of diethylnitrosamine (DEN), followed by dietary administration of the promoter sodium 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 nuclear antigen (PCNA). In addition, the level of ornithine decarboxylase (ODC), one of the rate‐limiting enzymes of polyamine metabolism induced by promoters, was analyzed. SMC and cysteine induced significant reduction in the areas of GST‐P‐positive foci. A significant reduction in the PCNA index was observed in the entire liver as well as in GST‐P‐positive areas. SMC also induced down‐regulation of the ODC enzyme activity. Thus, SMC and cysteine were found to inhibit the promotion stage of DEN‐induced hepatocarcinogenesis. No cocarcinogenic effects were evident on administration of either of these chemicals with NaPB.