von Hofe E, Newberne P M, Kennedy A R
Department of Pharmacology, University of Massachusetts Medical Center, Worcester 01655.
Carcinogenesis. 1991 Nov;12(11):2147-50. doi: 10.1093/carcin/12.11.2147.
Model systems in which carcinogenesis by given agents can be prevented or reduced offer a means of gaining insight into the mechanism(s) of action of carcinogens and the feasibility of chemoprevention in humans. In the current study, the ability of the soy-bean derived Bowman-Birk protease (BBI) to suppress esophageal carcinogenesis induced by N-nitrosomethylbenylamine (NMBzA) was examined. Esophageal lesions were produced in male Sprague-Dawley rats by i.p. injection of 2 mg/kg NMBzA twice weekly for 3 weeks. Groups receiving BBI were fed three tablets a week containing 180 mg BBI each in a mixture of Witepsol H15 and peanut butter for the duration of the experiment. The frequency of papillomas and carcinomas was reduced 45% in groups receiving BBI. Furthermore, the frequency of appearance of five separate characteristics of preneoplastic lesions was significantly reduced in the esophagi of BBI-treated animals. The most significant reduction was in the total number of lesions with simple hyperplasia. Groups receiving NMBzA and placebo tablets, containing only Witepsol H15 and peanut butter, did not display statistically significant differences in the frequency of esophageal lesions as compared to animals receiving NMBzA alone. These results demonstrate that BBI can effectively inhibit NMBzA-induced esophageal tumors when given in tablet form separate from the regular diet.
通过特定致癌物质诱导的致癌作用能够被预防或减轻的模型系统，为深入了解致癌物质的作用机制以及人类化学预防的可行性提供了一种手段。在当前的研究中，检测了源自大豆的鲍曼-伯克蛋白酶（BBI）抑制N-亚硝基甲基苄胺（NMBzA）诱导的食管癌发生的能力。通过每周两次腹腔注射2 mg/kg NMBzA，连续3周，在雄性Sprague-Dawley大鼠中诱导食管病变。在实验期间，接受BBI的组每周喂食三片含有180 mg BBI的片剂，这些片剂混合在Witepsol H15和花生酱中。接受BBI的组中乳头状瘤和癌的发生率降低了45%。此外，在接受BBI治疗的动物的食管中，癌前病变的五个独立特征的出现频率显著降低。最显著的降低是单纯增生性病变的总数。与仅接受NMBzA的动物相比，接受NMBzA和仅含有Witepsol H15和花生酱的安慰剂片剂的组在食管病变频率上没有显示出统计学上的显著差异。这些结果表明，当以与常规饮食分开的片剂形式给予时，BBI可以有效抑制NMBzA诱导的食管肿瘤。
