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

Jpn J Cancer Res. 2000 Aug;91(8):780-5. doi: 10.1111/j.1349-7006.2000.tb01013.x.


The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of rodent hepatocarcinogenesis 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens
  • Cysteine / analogs & derivatives*
  • Cysteine / therapeutic use*
  • Disease Models, Animal
  • Glutathione Transferase / metabolism
  • Immunohistochemistry
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / prevention & control*
  • Male
  • Ornithine Decarboxylase / metabolism
  • Phenobarbital
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Inbred F344


  • Carcinogens
  • Proliferating Cell Nuclear Antigen
  • S-methylcysteine
  • Glutathione Transferase
  • Ornithine Decarboxylase
  • Cysteine
  • Phenobarbital