Suzuki Isamu, Cho Young-Man, Hirata Tadashi, Toyoda Takeshi, Akagi Jun-Ichi, Nakamura Yasushi, Park Eun Young, Sasaki Azusa, Nakamura Takako, Okamoto Shigehisa, Shirota Koji, Suetome Noboru, Nishikawa Akiyoshi, Ogawa Kumiko
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu501-1193, Japan.
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
J Toxicol Pathol. 2016 Oct;29(4):237-246. doi: 10.1293/tox.2016-0037. Epub 2016 Jul 4.
To examine the effects of 4-methylthio-3-butenyl isothiocyanate on esophageal carcinogenesis, male 6-week-old F344 rats were subcutaneously injected with 0.5 mg/kg body weight -nitrosomethylbenzylamine three times per week for 5 weeks and fed a diet supplemented with 80 ppm 4-methylthio-3-butenyl isothiocyanate, equivalent to 6.05 mg/kg body weight/day for the initiation stage, 4.03 mg/kg body weight/day for the promotion stage, or 4.79 mg/kg body weight/day for all stages. Although the incidence of lesions was not affected by 4-methylthio-3-butenyl isothiocyanate treatment, the multiplicity of squamous cell papilloma in the esophagus was significantly decreased in rats in the 4-methylthio-3-butenyl isothiocyanate initiation stage group (1.13 ± 0.74), 4-methylthio-3-butenyl isothiocyanate promotion stage group (1.47 ± 0.99), and 4-methylthio-3-butenyl isothiocyanate all stage group (1.47 ± 1.13) as compared with rats treated with -nitrosomethylbenzylamine alone (3.00 ± 1.46). Immunohistochemical analysis revealed that 4-methylthio-3-butenyl isothiocyanate induced apoptosis, suppressed cell proliferation, and increased p21 expression when administered in the promotion phase. These modifying effects were not observed in the rats treated with 4-methylthio-3-butenyl isothiocyanate alone. Our results indicated that 4-methylthio-3-butenyl isothiocyanate may exert chemopreventive effects against -nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.
为研究4-甲硫基-3-丁烯基异硫氰酸酯对食管癌发生的影响，对6周龄雄性F344大鼠每周皮下注射3次0.5mg/kg体重的N-亚硝基甲基苄胺，持续5周，并给予添加了80ppm 4-甲硫基-3-丁烯基异硫氰酸酯的饲料，在启动阶段相当于6.05mg/kg体重/天，促进阶段为4.03mg/kg体重/天，或整个阶段为4.79mg/kg体重/天。虽然4-甲硫基-3-丁烯基异硫氰酸酯处理对病变发生率没有影响，但与单独用N-亚硝基甲基苄胺处理的大鼠（3.00±1.46）相比，4-甲硫基-3-丁烯基异硫氰酸酯启动阶段组（1.13±0.74）、4-甲硫基-3-丁烯基异硫氰酸酯促进阶段组（1.47±0.99）和4-甲硫基-3-丁烯基异硫氰酸酯整个阶段组（1.47±1.13）大鼠食管鳞状细胞乳头瘤的数量显著减少。免疫组织化学分析显示，在促进阶段给予4-甲硫基-3-丁烯基异硫氰酸酯可诱导细胞凋亡、抑制细胞增殖并增加p21表达。在单独用4-甲硫基-3-丁烯基异硫氰酸酯处理的大鼠中未观察到这些调节作用。我们的结果表明，4-甲硫基-3-丁烯基异硫氰酸酯可能对N-亚硝基甲基苄胺诱导的大鼠食管癌发生具有化学预防作用。
