Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl)nitrosamine in rats after initiation
Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl)nitrosamine in rats after initiation
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DOI：
10.1111/j.1349-7006.2003.tb01383.x
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发表时间：
2003-11-01
期刊：
影响因子：
5.7
通讯作者：
Hirose, M
中科院分区：
文献类型：
--
作者：
Okazaki, K;Umemura, T;Hirose, M
以前，我们报道，苯甲基异硫氰酸酯（BITC）强烈增强大鼠膀胱癌后开始与N-丁基-N-（4-羟丁基）亚硝胺（BBN），而有力地抑制BBN诱导的病变时，同时给予致癌剂。在本实验中，同时用BITC和低剂量BBN治疗对大鼠膀胱癌发生的后起始期的影响进行了检查。在用500 ppm BBN处理4周开始后，对20只6周龄F344雄性大鼠的组给予单独的25 ppm BBN、单独的基础饮食、或饮食中的100或1000 ppm BITC连同或不连同饮用水中的25 ppm BBN，持续36周，然后处死进行尸检。另外的组各由10只大鼠组成，类似地给予BITC或基础饮食连同或不连同25 ppm BBN，而不进行起始处理。在接受后续BBN暴露的启动组中，乳头状和结节性增生、异型增生和癌的发生率显著增加，并且以剂量依赖性方式与100和1000 ppm BITC联合治疗进一步增加。在非起始组中，仅在BBN处理的对照组和BBN/BITC 100 ppm处理组的每只大鼠中观察到癌。结果表明，同时治疗BITC和低剂量的BBN不抑制，而是增强大鼠膀胱癌发生后，适当的启动，并进一步表明，BITC可能是一个人类的危险因素，至少在高风险人群。
Previously we reported that benzyl isothiocyanate (BITC) strongly enhanced rat urinary bladder carcinogenesis after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), while potently inhibiting BBN-induction of lesions when given simultaneously with the carcinogen. In the present experiment, the effects of simultaneous treatment with BITC and low-dose BBN on the post-initiation period of rat urinary bladder carcinogenesis were examined. After treatment with 500 ppm BBN for 4 weeks for initiation, groups of 20, 6-week-old, F344 male rats were given 25 ppm BBN alone, basal diet alone, or 100 or 1000 ppm BITC in the diet together with or without 25 ppm BBN in their drinking water for 36 weeks and then killed for autopsy. Further groups consisting of 10 rats each were similarly given BITC or the basal diet together with or without 25 ppm BBN, without initiation treatment. In the initiated groups receiving subsequent BBN exposure, papillary and nodular hyperplasia, dysplasia and carcinoma incidences were significantly increased, and they were further increased by the combined treatment with 100 and 1000 ppm BITC in a dose-dependent manner. In the non-initiation groups, carcinomas were only observed in a single rat in each of the BBN-treated control and BBN/BITC 100 ppm treatment groups. The results indicate that simultaneous treatment with BITC and a low dose of BBN does not inhibit, but rather enhances rat urinary bladder carcinogenesis after appropriate initiation, and further suggest that BITC may be a human risk factor, at least in high-risk populations.