甲基丙烯酸环氧丙酯体外诱导的人胚肺成纤维细胞DNA链断裂  

DNA strand break induced by glycidyl methacrylate in human embryonic lung fibroblasts in vitro

作　　者：尹学钧[1] 许建宁[1] 王全凯[1] 宋文佳[1] 李忠生[1] 谢晓霜[1] 邹昌淇 方福德[2] 何凤生[1] 

机构地区：[1]中国预防医学科学院劳动卫生与职业病研究所,北京100050 [2]中国医学科学院基础医学研究所,北京100005

出　　处：《中国药理学与毒理学杂志》2000年第5期357-363,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目!(39840 0 17)

摘　　要：甲基丙烯酸环氧丙酯 (GMA)导致人胚肺成纤维细胞 (HELFs)恶性转化及其潜在致癌机理尚未阐明 .本研究用 0 .5- 5.0 mg· L-1的 GMA给体外培养的 HELFs染毒 2 h和 1 2 h,或用 5.0 mg· L-1的 GMA染毒 1 5min- 2 4 h,应用单细胞凝胶电泳技术 (彗星试验 )对 GMA引起的 HELFs DNA断裂作用进行了初步探讨 .琼脂糖凝胶电泳及流式细胞仪检测等方法观察了 GMA对细胞凋亡的诱导作用 .结果表明 ,GMA可导致染毒细胞 DNA发生剂量和时间依赖性链断裂 .用 5.0 mg· L-1的 GMA染毒后仅 1 h断裂作用即已显著 ,并随染毒时间延长而递增 ,至 2 4 h时损伤最为严重 .但在同样条件下未观察到 GMA对细胞凋亡的诱导作用 .结果提示 GMA导致的非凋亡性 DNA链断裂可能是其诱导The mechanisms of cell transfor- mation and potential carcinogenesis caused by glycidyl methacrylate(GMA) in human embryonic lung fibroblasts (HELFs) are not well understood. In this study,HEL Fs were exposed to 0 . 5 - 5 . 0 mg· L- 1 GMA in vitro for2 h and1 2 h or to5 .0 mg· L- 1 GMA for1 5 min- 2 4h and the induction of DNA strand break was studied using the single cell gel electrophoresis technique (comet assay) .Meanwhile,the induction of apoptosis in exposed HELFs was investi- gated by agarose gel electrophoresis and flow- cytometry assays.The results showed that GMA could cause DNA strand break in exposed cells in a dose- and time- dependent manner.The significant break was found as early as1 h after exposure and it was in- creased with time up to2 4h.The inducing effect of GMA on apoptotic response in HELFs,however,was not observed in the same conditions. These results strongly suggest that the induction of non- apoptotic DNA strand break be one of the important genetic events arisen at the early stage in the process of GMA- induced cell transfor- mation.

关 键 词：甲基丙烯酸环氧丙酯 DNA损伤 人胚肺成纤维细胞 

分 类 号：R135[医药卫生—劳动卫生]