Hirose M, Kawabe M, Shibata M, Takahashi S, Okazaki S, Ito N
First Department of Pathology, Nagoya City University, Medical School, Japan.
Carcinogenesis. 1992 Oct;13(10):1825-8. doi: 10.1093/carcin/13.10.1825.
Promotion effects of the o-dihydroxybenzene derivatives, protocatechuic acid (PCA), dopamine hydrochloride (DAH), dl-dopa and caffeic acid on forestomach and glandular stomach carcinogenesis were investigated in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 20 male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later than received diet containing 1.5% PCA, 1.5% DAH, 1.5% dl-dopa or 1% caffeic acid or basal diet alone for 51 weeks and then killed. Other groups of 10-15 rats were given PCA, DAH, dl-dopa or basal diet alone without the MNNG pretreatment. On histological assessment, the incidences of forestomach papillomas and squamous cell carcinomas were significantly enhanced in the group treated with caffeic acid (95 and 100%) as compared with the control values (35 and 10%). Although the incidence was not different, the number of papillomas per rat in the group given DAH (0.79 +/- 0.79) was also significantly increased (0.35 +/- 0.49). PCA and dl-dopa treatments did not modify the development of neoplastic lesions in the forestomach epithelium to any significant extent. None of the four chemicals enhanced glandular stomach carcinogenesis. The results thus demonstrated that whereas caffeic acid and DAH respectively, exert strong and weak promotion activity for rat forestomach carcinogenesis this promotion potential is not shared by all dihydroxybenzene derivatives. An influence of substituents in the para position in addition to the o-dihydroxy moiety is indicated.
研究了邻二羟基苯衍生物原儿茶酸（PCA）、盐酸多巴胺（DAH）、消旋多巴和咖啡酸对经N-甲基-N'-硝基-N-亚硝基胍（MNNG）预处理的大鼠前胃和腺胃癌变的促进作用。将20只雄性F344大鼠分为一组，单次胃内给予150 mg/kg体重的MNNG，1周后开始给予含1.5% PCA、1.5% DAH、1.5%消旋多巴或1%咖啡酸的饲料或仅给予基础饲料，持续51周，然后处死。其他10 - 15只大鼠的组在未进行MNNG预处理的情况下单独给予PCA、DAH、消旋多巴或基础饲料。组织学评估显示，与对照组（35%和10%）相比，咖啡酸处理组（95%和100%）的前胃乳头状瘤和鳞状细胞癌的发生率显著增加。虽然发生率没有差异，但给予DAH组每只大鼠的乳头状瘤数量（0.79±0.79）也显著增加（0.35±0.49）。PCA和消旋多巴处理在任何显著程度上均未改变前胃上皮肿瘤性病变的发展。这四种化学物质均未增强腺胃癌变。结果表明，咖啡酸和DAH分别对大鼠前胃癌变具有强促进活性和弱促进活性，但并非所有二羟基苯衍生物都具有这种促进潜力。这表明除了邻二羟基部分外，对位取代基也有影响。
