Cisplatin-induced genotoxic effects and endogenous glutathione levels in mice bearing ascites Dalton's lymphoma
Cisplatin-induced genotoxic effects and endogenous glutathione levels in mice bearing ascites Dalton's lymphoma
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DOI：
10.1016/s0027-5107(03)00005-8
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发表时间：
2003-05-15
影响因子：
2.3
通讯作者：
Prasad, SB
中科院分区：
文献类型：
--
作者：
Khynriam, D;Prasad, SB
顺式二氨二氯铂（II）（通常称为顺铂）给药小鼠24-96小时、30小时和10天，导致骨髓细胞以及道尔顿淋巴瘤（DL）细胞中出现染色体畸变、骨髓细胞中出现微核（MN）和精子头部异常，这表明顺铂在宿主中具有遗传毒性潜力。顺铂对骨髓和肿瘤细胞的染色体产生不同的影响。顺铂与谷胱甘肽（GSH）合成抑制剂L-丁硫氨酸（S，R）-亚砜亚胺（BSO）联合治疗，增强了这些顺铂诱导的遗传毒性作用，但补充谷胱甘肽水平与半胱氨酸，其前体，降低顺铂诱导的遗传毒性。细胞谷胱甘肽水平的降低可能促进细胞内蓄积和药物与DNA结合增加，从而增加遗传毒性参数的频率。这些研究结果支持谷胱甘肽作为一种重要的细胞内保护剂的可能参与，并表明其水平的差异可能是在不同的敏感性的细胞顺铂诱导的遗传毒性作用的小鼠腹水道尔顿淋巴瘤的因素之一。(C)2003 Elsevier Science B. V.保留所有权利。
cis-Diaminedichloroplatinum(II), commonly known as cisplatin, treatment of mice for 24-96, 30 h and 10 days caused the development of chromosomal aberrations in bone marrow cells as well as in Dalton's lymphoma (DL) cells, micronuclei (MN) in bone marrow cells and abnormalities in sperm heads, and it indicates the genotoxic potential of cisplatin in the host. Cisplatin exerts differential effects on the chromosomes of the bone marrow and tumor cells. Combination treatment of cisplatin with L-buthionine(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, enhanced these cisplatin-induced genotoxic effects, but supplementing glutathione level with cysteine, its precursor, reduced the cisplatin-induced genotoxicity. The reduction in cellular glutathione level may facilitate increased intracellular accumulation and binding of drug to DNA to enhance the frequency of genotoxicity parameters. These findings support the possible involvement of glutathione as an important intracellular protective agent and suggest that differences in its levels may be one of the factors in the varying sensitivity of cells to cisplatin-induced genotoxic effects in the mice bearing ascites Dalton's lymphoma. (C) 2003 Elsevier Science B.V. All rights reserved.