谷胱甘肽对甲醛所致DNA-蛋白质交联形成的促进作用

摘要

Our previous studies found that the glutathione(GSH) content in experimental animals reduced significantly with a dose-effect manner after the exposure of formaldehyde(FA)at the environmental levels. Moreover, the reduction of glutathione has no apparent protective effect for the genetic toxicity indicator DNA-protein crosslink (DPC) caused by formaldehyde. For an in-depth understanding on the combined effects of GSH and FA we undertook this study. Hela cells were used for experimental materials in vitro, the experimental group was divided into four groups: the control group, 250μM GSH Group,250μM formaldehyde group, 250μM formaldehyde and 250μM GSH combined group; Kun Ming mice were used for experimental materials in vivo, intraperitoneal injection was used for the exposure, which last for two weeks, the four experimental groups included control group, 1mM GSH group, 1mM formaldehyde group, and 1mM formaldehyde and 1mMGSH combined group. The in vitro and in vivo experimental results were similar, there were no significant differences between the control groups and GSH groups (p>0.05; p>0.05 ); the DPC induced by formaldehyde groups were significantly higher than that of control groups (p<0.01; p<0.05); the DPC induced by the combined groups were not only significantly higher than that of control groups (p<0.01; p<0.01) but also significantly higher than that of formaldehyde exposure group (p<0.05; p<0.01). The results suggest that GSH would not lead to the formation of DPC alone, but glutathione has a promotive effect on the DPC induced by formaldehyde. Meanwhile, the mechanism of the promotive effect was discussed in this paper; the authors suggest that the promotive effect of glutathione on formaldehyde molecules may be similar to the mechanism of glutathione on nitric molecules.%研究发现,在环境水平的甲醛染毒之后,动物体内的谷胱甘肽(GSH)含量会发生显著减少,并呈现剂量一效应关系.值得思索的是,GSH的减少对甲醛所致的遗传毒性指标DNA-蛋白质交联(DPC)没有明显的保护作用.为了深入探讨GSH与甲醛的联合作用,进行了体外和体内两项实验.体外实验以Hela细胞为实验材料,实验组分为4组:对照组、250μM GSH组、250μM甲醛组、250μM甲醛和250μM GSH联合作用组;体内实验以昆明小鼠为实验材料,采用腹腔注射方法连续染毒两周.实验组分为4组:对照组、1mM GSH组、1mM甲醛组、1mM甲醛和1mM GSH联合作用组.体外实验与体内实验结果表明,单独GSH染毒组所致DPC与试剂对照组之间没有统计学差异(p>0.05;p>0.05),甲醛染毒组所致DPC显著高于对照组(p<0.01;p<0.05),联合作用组所致DPC不但显著高于试剂对照组(p<0.01;p<0.01)而且还显著高于甲醛染毒组(p<0.05;p<0.01).结果提示,GSH单独作用不能诱导DPC形成,但是GSH对甲醛所致的DPC具有促进作用.同时论文对这种协同作用的发生机制进行了讨论,作者认为GSH与甲醛的协同作用,和GSH与一氧化氮的协同作用的分子机制类似.