Inhibitory Effects of S‐Methylcysteine and Cysteine on the Promoting Potential of Sodium Phenobarbital on Rat Liver Carcinogenesis

• Published in: Cancer science Vol. 91; no. 8; pp. 780 - 785
• Main Authors: Vijayaraghavan, Meenakshi, Wanibuchi, Hideki, Takada, Nobuyasu, Yano, Yoshihisa, Otani, Shuzo, Yamamoto, Shinji, Fukushima, Shoji
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2000; Japanese Cancer Association; John Wiley & Sons, Inc
• Subjects: Animals; Biological and medical sciences; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Chemical agents; Cysteine; Cysteine - analogs & derivatives; Cysteine - therapeutic use; Diethylnitrosamine; Disease Models, Animal; Enzymatic activity; Glutathione; Glutathione Transferase - metabolism; GST‐P; Hepatectomy; Immunohistochemistry; Liver; Liver Neoplasms - chemically induced; Liver Neoplasms - enzymology; Liver Neoplasms - metabolism; Liver Neoplasms - prevention & control; Male; Medical sciences; Ornithine; Ornithine decarboxylase; Ornithine Decarboxylase - metabolism; PCNA; Phenobarbital; Placenta; Proliferating cell nuclear antigen; Proliferating Cell Nuclear Antigen - metabolism; Rat hepatocarcinogenesis; Rats; Rats, Inbred F344; S‐Methylcysteine; Tumors; Cell proliferation; Animal model; Cysteine; Rat; Isozyme; Liver; Biological marker; Hepatic disease; Anticarcinogen; Antitumor promotor; Carcinogenesis; Organic sulfide; Glutathione transferase; Water solubility; Tumor promotion; Enzyme; Transferases; Rodentia; Malignant tumor; Phenobarbital sodium; Carcinogen; Vertebrata; Mammalia; Aminoacid; Animal; Digestive diseases; PCNA antigen
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.2000.tb01013.x

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.