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化学致癌物7,12-二甲基苯并[a]蒽对Wistar大鼠的毒性及硒的保护作用。

Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats.

作者信息

Kocdor Hilal, Cehreli Ruksan, Kocdor Mehmet Ali, Sis Banu, Yilmaz Osman, Canda Tulay, Demirkan Binnaz, Resmi Halil, Alakavuklar Mehmet, Harmancioglu Omer

机构信息

Institute of Oncology, Dokuz Eylul University, Izmir, Turkey.

出版信息

J Toxicol Environ Health A. 2005 May 14;68(9):693-701. doi: 10.1080/15287390590925438.

DOI:10.1080/15287390590925438
PMID:16020197
Abstract

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 microg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA-Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA-Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA-Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA.

摘要

7,12-二甲基苯并[a]蒽(DMBA)是一种多环芳烃(PAH),已被广泛用作引发乳腺癌发生及后续化学预防的工具。另一方面,硒(Se)在肿瘤学中具有潜在用途,因为这种元素具有抗癌和化学预防特性。含硒酶如谷胱甘肽过氧化物酶(GPx)在PAH代谢和解毒中起重要作用。在本研究中,给大鼠单次口服剂量的DMBA(12毫克)。在硒组中,大鼠从DMBA给药前2周开始每天通过灌胃接受20微克硒,并持续1周。DMBA给药120天后处死大鼠,并使用组织病理学和生化标准评估毒性。在研究期间,DMBA组有5只大鼠(30%)死亡,而DMBA-硒处理组未发生死亡。DMBA组恶性肿瘤发生率为33%,而DMBA-硒处理组未发生恶性肿瘤。组织病理学检查发现一些炎症变化而非上皮变化。与单独使用DMBA相比,DMBA-硒处理组的GPx活性和血尿素氮水平较高,肾脏GST活性较低。总之,硒似乎能有效预防一些与DMBA相关的不良反应。

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