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砷诱导的人胎儿肺成纤维细胞中与DNA-蛋白质交联相关的DNA链断裂。

Arsenic-induced DNA-strand breaks associated with DNA-protein crosslinks in human fetal lung fibroblasts.

作者信息

Dong J T, Luo X M

机构信息

Cancer Institute, Chinese Academy of Medical Sciences, Beijing.

出版信息

Mutat Res. 1993 Jun;302(2):97-102. doi: 10.1016/0165-7992(93)90010-s.

DOI:10.1016/0165-7992(93)90010-s
PMID:7684511
Abstract

Sodium arsenite (As)-induced DNA damage was measured in human fetal lung fibroblasts (2BS cells) by an alkaline elution technique and a fluorometric DNA assay. Sodium arsenite at 1-5 microM produced DNA-protein crosslinks, while at 10 microM this effect was not observed. Deproteinization of DNA-protein complexes revealed protein-associated DNA-strand breaks. Both DNA-protein crosslinks and DNA-strand breaks were concentration-dependent; 3 microM As was the most efficient dose. Arsenic mediated DNA-protein interactions may play a major role in arsenic carcinogenesis, and the induced protein-associated DNA-strand breaks could provide an explanation for chromosome aberrations and sister-chromatid exchanges induced by arsenic in vivo and in vitro.

摘要

采用碱性洗脱技术和荧光DNA分析法,检测亚砷酸钠(As)诱导的人胚肺成纤维细胞(2BS细胞)中的DNA损伤。1-5微摩尔的亚砷酸钠可产生DNA-蛋白质交联,而在10微摩尔时未观察到这种效应。DNA-蛋白质复合物的脱蛋白作用显示出与蛋白质相关的DNA链断裂。DNA-蛋白质交联和DNA链断裂均呈浓度依赖性;3微摩尔的As是最有效的剂量。砷介导的DNA-蛋白质相互作用可能在砷致癌过程中起主要作用,并且诱导产生的与蛋白质相关的DNA链断裂可以解释砷在体内和体外诱导的染色体畸变和姐妹染色单体交换。

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