Sugie S, Okamoto K, Okumura A, Tanaka T, Mori H
Department of Pathology, Gifu University School of Medicine, Japan.
Carcinogenesis. 1994 Aug;15(8):1555-60. doi: 10.1093/carcin/15.8.1555.
The effects of two aromatic thiocyanates, benzyl thiocyanate (BTC) and benzyl isothiocyanate (BITC), on methylazoxymethanol (MAM) acetate-induced intestinal carcinogenesis were examined using female ACI/N rats. Starting at 5 weeks of age, animals were fed diets containing 100 or 400 p.p.m. BTC, 400 p.p.m. BITC or a control diet. At 6 weeks of age, all animals were treated with i.p. injections of MAM acetate (25 mg/kg body wt, once weekly for 3 weeks) or saline. Animals fed experimental diets were changed to the control diet from a week after the last carcinogen treatment. Three groups of animals fed the control diet were switched to 100 p.p.m. BTC, 400 p.p.m. BTC or 400 p.p.m. BITC diet from a week after carcinogen treatment. Animals given the high-dose BTC diet at the initiation and the post-initiation phase showed smaller incidence (5% and 17%) and multiplicity (0.05 +/- 0.21 and 0.17 +/- 0.37) of tumours in small intestine compared with those of rats exposed to the carcinogen alone (61% and 1.06 +/- 1.18). The incidence and multiplicity of tumors in small intestine (21% and 0.32 +/- 0.73) and the incidence of colon tumors of rats given BITC in the initiation phase (47%) were significantly lower than those of animals treated with carcinogen alone (61%, 1.06 +/- 1.18 and 83%). Bromodeoxyuridine labeling indices of the intestinal mucosal cells were measured. The labeling indices were reduced by BTC and BITC exposure at initiation phase in both small intestine and colon. The results of measurement of labeling indices correlated with the decreased tumor incidence and multiplicity in the intestine. These data suggest that BTC and BITC could be promising chemopreventive agents for human intestinal neoplasia.
使用雌性 ACI/N 大鼠研究了两种芳香族硫氰酸盐，苄基硫氰酸盐（BTC）和苄基异硫氰酸盐（BITC）对乙酸甲基偶氮甲醇（MAM）诱导的肠道癌变的影响。从 5 周龄开始，给动物喂食含 100 或 400 ppm BTC、400 ppm BITC 的饲料或对照饲料。6 周龄时，所有动物腹腔注射乙酸 MAM（25 mg/kg 体重，每周一次，共 3 周）或生理盐水。喂食实验饲料的动物在最后一次致癌物处理后一周改为对照饲料。三组喂食对照饲料的动物在致癌物处理后一周改为 100 ppm BTC、400 ppm BTC 或 400 ppm BITC 饲料。在启动期和启动后期给予高剂量 BTC 饲料的动物，与单独暴露于致癌物的大鼠相比，小肠肿瘤的发生率（5%和 17%）和多发性（0.05±0.21 和 0.17±0.37）较低（单独暴露于致癌物的大鼠为 61%和 1.06±1.18）。启动期给予 BITC 的大鼠小肠肿瘤的发生率和多发性（21%和 0.32±0.73）以及结肠肿瘤的发生率（47%）显著低于单独用致癌物处理的动物（61%、1.06±1.18 和 83%）。测量了肠黏膜细胞的溴脱氧尿苷标记指数。在启动期，BTC 和 BITC 暴露均降低了小肠和结肠的标记指数。标记指数的测量结果与肠道肿瘤发生率和多发性的降低相关。这些数据表明，BTC 和 BITC 可能是有前景的人类肠道肿瘤化学预防剂。
