Sugie S, Okamoto K, Ohnishi M, Makita H, Kawamori T, Watanabe T, Tanaka T, Nakamura Y K, Nakamura Y, Tomita I, Mori H
Department of Pathology, Institute of Laboratory Animals, Gifu University School of Medicine, Tsukasa-machi.
Jpn J Cancer Res. 1997 Jan;88(1):5-11. doi: 10.1111/j.1349-7006.1997.tb00294.x.
Modifying effects of S-methyl methanethiosulfonate (MMTS) on diethylnitrosamine (DEN)-initiated and phenobarbital (PB)-promoted hepatocarcinogenesis were examined in rats. Five-week-old male F344 rats were divided into 8 groups. After a week, groups 1-5 were given DEN (100 mg/kg body weight, i.p.) once a week for 3 weeks, whereas groups 6-8 received vehicle treatment. Group 2 was given 100 ppm MMTS containing diet in the initiation phase. From 4 weeks after the start of experiment, groups 3 and 5 were fed MMTS, and groups 1-3 and 7 received drinking water containing 500 ppm PB. Group 6 was given MMTS diet alone throughout the experiment (24 weeks). The incidences of hepatocellular adenoma and total liver tumors were significantly smaller in group 3 than those of group 1. The average numbers of hepatocellular adenoma, carcinoma and total tumors in group 3 were significantly smaller than in group 1. Glutathione S-transferase placental form-positive foci were also significantly decreased by MMTS treatment in the promotion phase. MMTS treatment in the initiation or promotion phase reduced ornithine decarboxylase activity in the liver of rats given DEN. The antioxidant activity against lipid peroxidation of MMTS was confirmed in tests with rabbit erythrocyte membrane ghosts or rat hepatocytes. These results suggest that MMTS is a promising chemopreventive agent for liver neoplasia when concurrently administered with PB.
研究了甲硫基甲烷磺酸甲酯（MMTS）对二乙基亚硝胺（DEN）启动和苯巴比妥（PB）促进的大鼠肝癌发生的修饰作用。将5周龄雄性F344大鼠分为8组。一周后，第1 - 5组每周一次腹腔注射DEN（100 mg/kg体重），共3周，而第6 - 8组接受溶剂处理。第2组在启动阶段给予含100 ppm MMTS的饲料。从实验开始4周后，第3组和第5组喂食MMTS，第1 - 3组和第7组饮用含500 ppm PB的水。第6组在整个实验（24周）中单独给予MMTS饲料。第3组肝细胞腺瘤和肝脏肿瘤总数的发生率显著低于第1组。第3组肝细胞腺瘤、癌和肿瘤总数的平均数显著低于第1组。在促进阶段，MMTS处理也显著减少了谷胱甘肽S - 转移酶胎盘型阳性灶。在启动或促进阶段进行MMTS处理可降低给予DEN的大鼠肝脏中的鸟氨酸脱羧酶活性。在兔红细胞膜鬼臼或大鼠肝细胞试验中证实了MMTS对脂质过氧化的抗氧化活性。这些结果表明，当与PB同时给药时，MMTS是一种有前途的肝脏肿瘤化学预防剂。
