Possible carcinogenic risks of copper gluconate and their prevention by co-administered green tea catechins evaluated by a rat medium-term multi-organ carcinogenicity bioassay protocol
Possible carcinogenic risks of copper gluconate and their prevention by co-administered green tea catechins evaluated by a rat medium-term multi-organ carcinogenicity bioassay protocol
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DOI：
10.1016/j.fct.2008.01.024
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发表时间：
2008-05-01
影响因子：
4.3
通讯作者：
Nakae, Dai
中科院分区：
文献类型：
--
作者：
Abe, Masayoshi;Suzuki, Noriko;Nakae, Dai
使用大鼠中期多器官致癌性生物测定方案评估葡萄糖酸铜、绿茶儿茶素及其组合暴露的致癌风险。雄性 BrlHan:WIST@Jcl (GALAS) 大鼠给予 N-亚硝基二乙胺 (DEN)、N-甲基亚硝基脲 (MNU)、1,2-二甲基肼 (DMH)、N-丁基-N-(4-羟丁基)亚硝胺 (BBN) 和 2,2'-二羟基-二正丙基亚硝胺 (DHPN)，总共 4 周的多次启动期（DMBDD 治疗）。然后，从一周后开始，通过以5000 ppm的浓度与饮用水混合，给大鼠喂食含有浓度为03、10、3003、3000或6000 ppm的葡萄糖酸铜的饮食，并联合或不联合给予儿茶素。所有幸存者在第 29 周结束时被处死。300 ppm 或更高的葡萄糖酸铜显着增加了推定的肿瘤前、谷胱甘肽 S-转移酶胎盘形式阳性、肝脏病变的数量。此外，6000 ppm的葡萄糖酸铜显着增加了前胃增生的发生率和程度。儿茶素本身不产生任何作用，但却抑制了葡萄糖酸铜的这些作用。目前的结果表明，高剂量的葡萄糖酸铜可能对肝脏和前胃有致癌风险，同时服用绿茶儿茶素可能会起到预防作用。 (c) 2008 Elsevier Ltd. 保留所有权利。
Carcinogenic risks of copper gluconate, green tea catechins and their combined exposure were evaluated using a rat medium-term multi-organ carcinogenicity bioassay protocol. Male BrlHan:WIST@Jcl (GALAS) rats were given N-nitrosodiethylamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). Rats were then given a diet containing copper gluconate at a concentration of 03 10, 3003 3000 or 6000 ppm with or without a co-administration of catechins starting I week later by admixing in the drinking water at a concentration of 5000 ppm. All survivors were sacrificed at the end of week 29. Number of putatively preneoplastic, glutathione S-transferase placental form-positive, liver lesions significantly increased by copper gluconate of 300 ppm or greater. In addition, both incidence and grade of hyperplasia in the forestomach significantly increased by copper gluconate of 6000 ppm. Catechins, exerting no effects by themselves, inhibited these effects of copper gluconate. The present results indicate that copper gluconate may possess carcinogenic risks for the liver and forestomach at its high dose level, and that co-administered green tea catechins may exert preventive effects. (c) 2008 Elsevier Ltd. All rights reserved.