Vijayaraghavan M, Wanibuchi H, Takada N, Yano Y, Otani S, Yamamoto S, Fukushima S
First Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
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.
在伊藤先前开发的中期生物测定中，研究了S-甲基半胱氨酸（SMC）和半胱氨酸对啮齿动物肝癌发生促进阶段的影响。通过单剂量二乙基亚硝胺（DEN）诱导启动，两周后通过饮食给予促癌剂苯巴比妥钠（NaPB），持续6周。在第3周对所有动物进行部分肝切除术。通过分析两种致癌标志物，即谷胱甘肽S-转移酶胎盘型（GST-P）阳性灶的数量和增殖细胞核抗原（PCNA），评估抑制潜力。此外，还分析了促癌剂诱导的多胺代谢限速酶之一鸟氨酸脱羧酶（ODC）的水平。SMC和半胱氨酸可使GST-P阳性灶面积显著减少。在整个肝脏以及GST-P阳性区域均观察到PCNA指数显著降低。SMC还诱导ODC酶活性下调。因此，发现SMC和半胱氨酸可抑制DEN诱导的肝癌发生的促进阶段。将这些化学物质中的任何一种与NaPB一起给药时，均未发现明显的协同致癌作用。
