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 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.
Vijayaraghavan
M
M
First Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
Wanibuchi
H
H
Takada
N
N
Yano
Y
Y
Otani
S
S
Yamamoto
S
S
Fukushima
S
S
D000818:Animals; D002273:Carcinogens; D003545:Cysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010634:Phenobarbital; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; C008425:S-methylcysteine; D005982:Glutathione Transferase; D009955:Ornithine Decarboxylase; D003545:Cysteine; D010634:Phenobarbital