A comparative study of dimethylhydrazine regioisomers and the methylazoxymethanol metabolite of 1,1- and 1,2-dimethylhydrazine in relation to transformation in human fibroblasts.
A comparative study of dimethylhydrazine regioisomers and the methylazoxymethanol metabolite of 1,1- and 1,2-dimethylhydrazine in relation to transformation in human fibroblasts.
复制标题
二甲基肼区域异构体以及 1,1- 和 1,2-二甲基肼的甲基偶氮甲醇代谢物与人成纤维细胞转化相关的比较研究。
DOI：
10.1016/0304-3835(85)90136-3
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发表时间：
1985
期刊：
影响因子：
9.7
通讯作者：
Milo,GE
中科院分区：
文献类型：
--
作者：
Kumari,HL;Kamat,PL;D'Ambrosio,SM;Witiak,DT;Milo,GE
比较分析了二甲基肼（DMH）的两种区域异构体（1，1-DMH和1，2-DMH）及其代谢产物甲基偶氮甲醇（MAM）的乙酸酯衍生物（A）对人包皮成纤维细胞的细胞毒性、转化效率、碱不稳定位点（ALS）诱导和DNA甲基化。MAMA、1，1-DMH和1，2-DMH的有效ED 50细胞毒剂量分别为0.056、6.83和6.30 mM。MAMA和1，1-DMH是比1，2-DMH更有效的变压器。然而，嘌呤甲基化占所有3种药物与DNA相关的总放射性标记的不到1%。1，2-DMH、1，1-DMH和MAMA诱导的O 6 MeGua/N7 MeGua比值分别为0.04、0.32和0.18。只有MAMA在转化剂量下诱导可测量的碱不稳定病变。这些结果表明，其他机制可能在肼类似物引发转化事件中发挥作用。
Comparative analysis of the cytotoxicity, transformation efficiency, induction of alkali labile sites (ALS) and DNA methylation in human foreskin fibroblasts was carried out with two dimethylhydrazine (DMH) regio-isomers (1,1-DMH and 1,2-DMH) and the acetate (A) derivative of the metabolite methylazoxymethanol (MAM) of 1,2-DMH. Effective ED50cytotoxic doses for MAMA, 1,1-DMH and 1,2-DMH were 0.056, 6.83 and 6.30 mM, respectively. MAMA and 1,1-DMH were more effective transformers than 1,2-DMH. However, methylation of purines accounted for less than 1% of the total radiolabel associated with DNA for all 3 agents. 1,2-DMH, 1,1-DMH and MAMA induced O6MeGua/N7MeGua ratio of 0.04, 0.32 and 0.18, respectively. Only MAMA induced measurable alkali labile lesions at transforming doses. These results suggest that other mechanisms may play a role in the initiation of transformation events by hydrazine analogues.