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博来霉素诱导的人结肠黏膜细胞DNA损伤及维生素E的保护作用

DNA damage in human colonic mucosa cells induced by bleomycin and the protective action of vitamin E.

作者信息

Woźniak Katarzyna, Arabski Michał, Małecka-Panas Ewa, Drzewoski Józef, Błasiak Janusz

机构信息

Department of Molecular Genetics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.

出版信息

Cell Mol Biol Lett. 2004;9(1):31-45.

Abstract

Using the alkaline comet assay, we showed that bleomycin at 0.1-5 microg/ml induced DNA strand breaks and/or alkali-labile sites, measurable as the comet tail moment, in human colonic mucosa cells. This DNA damage was completely repaired during a 120-minute post-treatment incubation of the cells. Post-treatment of the bleomycin-damaged DNA with 3-methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing alkylated bases, gave rise to a significant increase in the extent of DNA damage, indicating that the drug could induce alkylative bases in DNA. We did not observe any change in the comet tail moment in the presence of catalase. Vitamin E ((+)-alpha -tocopherol) decreased DNA damage induced by bleomycin. The results obtained suggest that hydrogen peroxide might not be involved in the formation of DNA lesions induced by bleomycin in the colonic mucosa cells.

摘要

使用碱性彗星试验,我们发现,浓度为0.1 - 5微克/毫升的博来霉素可诱导人结肠黏膜细胞出现DNA链断裂和/或碱不稳定位点,可通过彗星尾矩进行测量。这种DNA损伤在细胞处理后的120分钟孵育期内完全修复。用识别烷基化碱基的3 - 甲基腺嘌呤 - DNA糖基化酶II(AlkA)对博来霉素损伤的DNA进行处理后,DNA损伤程度显著增加,表明该药物可在DNA中诱导烷基化碱基。在过氧化氢酶存在的情况下,我们未观察到彗星尾矩有任何变化。维生素E((+)-α-生育酚)可减少博来霉素诱导的DNA损伤。所得结果表明,过氧化氢可能不参与博来霉素在结肠黏膜细胞中诱导的DNA损伤的形成。

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