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硒代蛋氨酸对可移植性小鼠淋巴瘤的抑制作用:对肝脏药物代谢酶的思考

Selenomethionine in the inhibition of a transplantable murine lymphoma: reflection on hepatic drug metabolizing enzymes.

作者信息

Rana M P, Sardar S, Chatterjee M

机构信息

Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.

出版信息

Tumour Biol. 1996;17(2):102-9. doi: 10.1159/000217973.

Abstract

This study attempts to determine whether selenomethionine treatment can improve the survival time of mice inoculated with Dalton's lymphoma (DL) and thereby to identify phase/phases of the neoplastic processes at which selenium exerts its maximal action as an anticancer agent. Accordingly, a maximum of 30.76 and 143% increase in survival was brought about by treatment of selenomethionine prior to lymphoma transplantation, in comparison to mice receiving selenomethione supplementation concurrently with inoculation of DL, and those tumor-bearing mice receiving no supplementation, respectively. Beneficiality of selenomethionine has also been studied by monitoring the continuous changes brought about by this compound on hepatic total cytochrome P-450 and b5 content, NADPH cytochrome c reductase, UDP glucuronyl transferase and glutathione S-transferase (GST) activities. These are important biotransformation enzymes and are altered significantly in neoplasia. The drastic increase in all the markers studied, excepting GST, was effectively counteracted by selenomethionine treatment (more before than concurrently), which sufficiently delayed and controlled the increase in those xenobiotic indices. The 112 and 78.78% induction in GST activity brought about by prior and concurrent treatment of selenomethionine, respectively, confirms the fact that inducers of GSTs are often antitumorigenic.

摘要

本研究试图确定硒代蛋氨酸治疗是否能提高接种道尔顿淋巴瘤(DL)小鼠的存活时间,从而确定肿瘤发生过程中硒作为抗癌剂发挥最大作用的阶段。因此,与在接种DL的同时补充硒代蛋氨酸的小鼠以及未接受补充的荷瘤小鼠相比,在淋巴瘤移植前用硒代蛋氨酸治疗使存活率分别提高了30.76%和143%。通过监测该化合物对肝脏总细胞色素P-450和b5含量、NADPH细胞色素c还原酶、UDP葡萄糖醛酸转移酶和谷胱甘肽S-转移酶(GST)活性的持续变化,也研究了硒代蛋氨酸的益处。这些都是重要的生物转化酶,在肿瘤形成过程中会发生显著改变。除GST外,所研究的所有标志物的急剧增加都被硒代蛋氨酸治疗有效抵消(治疗前比同时治疗时更有效),这充分延迟并控制了这些外源性指标的增加。硒代蛋氨酸治疗前和同时治疗分别使GST活性诱导112%和78.78%,这证实了GST诱导剂通常具有抗肿瘤作用这一事实。

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