二甲基肼区域异构体以及1,1-二甲基肼和1,2-二甲基肼的甲基氧化偶氮甲醇代谢物在人成纤维细胞中转化的比较研究。

A comparative study of dimethylhydrazine regioisomers and the methylazoxymethanol metabolite of 1,1- and 1,2-dimethylhydrazine in relation to transformation in human fibroblasts.

作者信息

Kumari H L, Kamat P L, D'Ambrosio S M, Witiak D T, Milo G E

出版信息

Cancer Lett. 1985 Dec;29(3):265-75. doi: 10.1016/0304-3835(85)90136-3.

Abstract

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) regioisomers (1,1-DMH and 1,2-DMH) and the acetate (A) derivative of the metabolite methylazoxymethanol (MAM) of 1,2-DMH. Effective ED50 cytotoxic 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.

摘要

利用两种二甲基肼（DMH）区域异构体（1,1-DMH和1,2-DMH）以及1,2-DMH代谢产物甲基偶氮甲醇（MAM）的乙酸酯（A）衍生物，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）诱导及DNA甲基化进行了比较分析。MAMA、1,1-DMH和1,2-DMH的有效ED50细胞毒性剂量分别为0.056、6.83和6.30 mM。MAMA和1,1-DMH比1,2-DMH更有效地诱导细胞转化。然而，对于所有3种试剂，嘌呤甲基化占与DNA相关的总放射性标记的比例不到1%。1,2-DMH、1,1-DMH和MAMA诱导的O6MeGua/N7MeGua比值分别为0.04、0.32和0.18。只有MAMA在转化剂量下诱导了可测量的碱不稳定损伤。这些结果表明，其他机制可能在肼类似物引发转化事件中起作用。