有机砷化合物二甲基次胂酸促进NCI-黑-赖特雄性大鼠膀胱癌发生

Promotion of NCI-Black-Reiter male rat bladder carcinogenesis by dimethylarsinic acid an organic arsenic compound.

作者信息

Li W, Wanibuchi H, Salim E I, Yamamoto S, Yoshida K, Endo G, Fukushima S

机构信息

First Department of Pathology, Osaka City University Medical School, Osaka, Japan.

出版信息

Cancer Lett. 1998 Dec 11;134(1):29-36. doi: 10.1016/s0304-3835(98)00237-7.

DOI:10.1016/s0304-3835(98)00237-7

PMID:10381127

Abstract

Dimethylarsinic acid (DMAA) is a major metabolite of inorganic arsenicals in mammals. In the present study, we investigated its promoting effects on urinary bladder carcinogenesis in NCI-Black-Reiter (NBR) rats, which lack alpha2u-globulin synthesizing ability. Male 9-14-week-old NBR rats were treated sequentially with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 4 weeks and then given 100 ppm DMAA in their drinking water (group 1) for 32 weeks. Induction of preneoplastic lesions (papillary or nodular hyperplasia) in this DMAA-treated group was significantly increased as compared to the carcinogen alone control group (P < 0.01). The development of carcinomas was also enhanced and a significant increase in the 5-bromo-2'-deoxyuridine (BrdU) labeling index of the urinary bladder epithelial cells was observed for the DMAA treatment group. These results indicate that DMAA has promoting effects on urinary bladder carcinogenesis even in NBR rats, so its effects are not dependent on the presence of alpha2u-globulin.

摘要

二甲基胂酸（DMAA）是哺乳动物体内无机砷化合物的主要代谢产物。在本研究中，我们调查了其对缺乏α2u-球蛋白合成能力的NCI-黑雷特（NBR）大鼠膀胱致癌作用的促进效应。9至14周龄的雄性NBR大鼠先连续4周接受0.05%的N-丁基-N-（4-羟丁基）亚硝胺（BBN）处理，然后在其饮用水中给予100 ppm的DMAA（第1组），持续32周。与仅使用致癌物的对照组相比，该DMAA处理组中癌前病变（乳头状或结节状增生）的诱导显著增加（P < 0.01）。癌的发生也有所增强，并且在DMAA处理组中观察到膀胱上皮细胞的5-溴-2'-脱氧尿苷（BrdU）标记指数显著增加。这些结果表明，即使在NBR大鼠中，DMAA对膀胱致癌作用也有促进效应，因此其作用不依赖于α2u-球蛋白的存在。