氯化镉对人全血细胞程序外DNA合成的影响

Effect of Cadmium Chloride on the Unscheduled DNA Synthesis in Whole Blood Cells of Human

背景与目的:进一步明确镉对人类细胞DNA的损伤效应以及对损伤修复的干扰作用。材料与方法:利用简化人全血细胞检测法研究了CdCl2诱导人全血细胞(主要是淋巴细胞和单核细胞参与反应)程序外:DNA合成(unscheduled DNA synthesis,UDS)的能力及其对该细胞经N-甲基-N'-硝基-亚硝基胍(MNNG)或紫外线(UV)处理后DNA修复合成的影响。结果:0.1-10 μmol/L的CdCl2单独作用,细胞DNA修复合成前体物3H-TdR的掺入量与镉浓度量呈高度正相关的剂量-效应关系,其中10μmol／L剂量组与对照组相比差异有显著性;CdCl2在对人全血细胞UDS无明显诱导的剂量水平下即可使MNNG作用后DNA的修复合成受抑;与之相反,1μmol／L CdCl2与UV共同作用对人全血细胞UDS的诱导存在明显的协同作用。结论:较高浓度的镉对DNA具有损伤作用;而在较低浓度下,镉干扰DNA修复过程的作用较明显。上述直接和间接的遗传毒作用可能是镉致癌的机制之一。

BACKGROUND & AIM: To make further understanding in the action of Cd to inhibit the repair of DNA lesions in human cells. MATERIAL AND METHODS: The simplified method of unscheduled DNA synthesis(UDS) test with human whole blood cells (lymphocytes and monocytes were the main cell types involved in the test) was adopted to investigate the effect of CdCl2 on the repair processes of DNA damage induced by N-methyl-N' -nitro-N-nitrosoguanidine (MNNG)and ultraviolet(UV) .RESULTS: Treatment of human blood cells with Cd caused a dose-dependent increase in the amounts of 3H-TdR incorporated in DNA through UDS, but the cpm value was significantly elevated only at 10 μmol/L Cd dose as compared with the negative control, which indicated apparent DNA damage induced by Cd . MNNG- induced UDS was weakened to some extent by Cd dose from 0.1 to 10μmol/L,the remarkable inhibition was observed at Cd concentration of 1 μmol/L, while treatment with Cd of this concentration alone did not induce positive UDS.In contrast to MNNG, UV-induced UDS was strongly enhanced by 1 μmol/L CdCl2.The analysis of variance showed an evident synergistic interaction between this dose of Cd and UV. CONCLUSION: Cd itself can induce DNA damage at relatively high dose, while the lower Cd dose may interfere with DNA repair process and these direct and indirect genotoxic mechanisms may be involved in the carcinogenicity of Cd compounds.