Jianhua Zhou, Lian Xue, Shuanlai Zheng, Juan Du, Shuanxi Yang
Department of Occupational and Environmental Health, School of Radiation Medicine and Public Health, Soochow University, Suzhou, China.
J Occup Health. 2006 Mar;48(2):93-9. doi: 10.1539/joh.48.93.
Cadmium is a potential carcinogenic environmental and occupational pollutant. A wide variety of mutagens have been shown to cause DNA damage, but it is not yet clear whether the DNA damage is relative to inducement of mutations. DNA damage and the formation of mutations at the hypoxanthine guanine phosphoribosyl trans ferase (HPRT) induced by cadmium chloride (CdCl(2)) were investigated with rat lymphocytes and V79 Chinese hamster lung cells. The hprt mutant frequency (MF) assay was used as the method to measure gene mutation in the rat lymphocytes and V79 cells exposed to CdCl(2), and comet assay analysis was performed to detect DNA lesion and repair in CdCl(2)-induced V79 cells. The results showed that CdCl(2) treatment caused a strong genotoxic effect and a marginal effect on the frequency of gene mutations. The hprt mutant frequencies in the rat lymphocytes and V79 cells exposed to CdCl(2) were statistically higher than those of the negative control. There was statistical significance in TL, TD and percentage of comet cell with tails. CdCl(2) treatment can induce DNA single-strand breaks. There was a dose-dependent increase between CdCl(2) and DNA lesion. After cells were treated with CdCl(2) and hydrogen peroxide (H(2)O(2)), the TL and TD declined with repair time increasing, which indicated that DNA damages were repaired gradually. However, DNA repair with treatment of CdCl(2) was slower than that of H(2)O(2) in V79 cells, which suggests that CdCl(2) affected DNA repair of damaged cells. The study also showed that the hprt MF and comet assay can be used for genotoxicity testing of heavy metals. DNA damage detected with the comet assay may be relative to mutagenesis.
镉是一种潜在的致癌性环境和职业污染物。多种诱变剂已被证明可导致DNA损伤,但DNA损伤是否与突变诱导相关尚不清楚。用大鼠淋巴细胞和V79中国仓鼠肺细胞研究了氯化镉(CdCl₂)诱导的次黄嘌呤鸟嘌呤磷酸核糖转移酶(HPRT)处的DNA损伤和突变形成。采用hprt突变频率(MF)测定法测量暴露于CdCl₂的大鼠淋巴细胞和V79细胞中的基因突变,并进行彗星试验分析以检测CdCl₂诱导的V79细胞中的DNA损伤和修复情况。结果表明,CdCl₂处理产生了强烈的遗传毒性作用以及对基因突变频率的轻微影响。暴露于CdCl₂的大鼠淋巴细胞和V79细胞中的hprt突变频率在统计学上高于阴性对照。在尾长(TL)、尾矩(TD)和彗星尾细胞百分比方面存在统计学意义。CdCl₂处理可诱导DNA单链断裂。CdCl₂与DNA损伤之间存在剂量依赖性增加。在用CdCl₂和过氧化氢(H₂O₂)处理细胞后,TL和TD随修复时间增加而下降,这表明DNA损伤逐渐得到修复。然而,在V79细胞中,CdCl₂处理后的DNA修复比H₂O₂处理后的慢,这表明CdCl₂影响受损细胞的DNA修复。该研究还表明,hprt MF和彗星试验可用于重金属的遗传毒性测试。用彗星试验检测到的DNA损伤可能与诱变作用相关。