Jiang Wei, Lu Yezheng, Chen Zhijian, Chen Shijie, Zhang Meibian, Jin Lifen, Lou Jianlin, He Jiliang
Zhejiang University, Medical College, Institute of Environmental Medicine, Hangzhou 310058, Zhejiang, People's Republic of China.
Toxicology. 2008 Oct 30;252(1-3):113-7. doi: 10.1016/j.tox.2008.07.057. Epub 2008 Aug 5.
The results of our previous investigation for workers occupationally exposed to vincristine (VCR) indicated that the genetic damage was detectable with comet assay, cytokinesis-block micronucleus (CBMN) assay and housekeeping gene mutation tests. In order to determine the results of above investigation and to inquire further the characteristics of genotoxicity of VCR, the cytogenetic effects of VCR on human lymphocytes were assessed with comet assay, CBMN assay and T-cell receptor (TCR) gene mutation test in vitro. The lymphocytes from two healthy donors were incubated for 24h at doses of 0.00, 0.01, 0.02, 0.04, and 0.08microgml(-1) VCR. The results of the present experiment showed that VCR not only could induce DNA damage, increase significantly micronucleus frequencies and the apoptotic cell ratios and decrease the nuclear division index (NDI) with dose-response relationship, but also could produce nucleoplasmic bridges (NPBs), a biomarker of DNA misrepair and/or telomere end-fusions and nuclear buds (NBUDs), a biomarker of elimination of amplified DNA and/or DNA repair complexes. Moreover, VCR could enhance TCR gene mutation frequency (Mf-TCR) of human lymphocytes. There was good correlation between the parameters (mean tail length, mean tail moment, micronucleus frequency, micronucleated frequency and Mf-TCR). The results of present study supported the results of our previous investigation for workers occupationally exposed to VCR, and the genotoxicity of VCR was determined at the different genetic end-points in vitro.
我们之前针对职业性接触长春新碱（VCR）的工人进行的调查结果表明，通过彗星试验、胞质分裂阻滞微核（CBMN）试验和管家基因突变试验可检测到遗传损伤。为了确定上述调查结果并进一步探究VCR的遗传毒性特征，我们在体外通过彗星试验、CBMN试验和T细胞受体（TCR）基因突变试验评估了VCR对人淋巴细胞的细胞遗传学效应。将来自两名健康供体的淋巴细胞分别在0.00、0.01、0.02、0.04和0.08μg/ml的VCR剂量下孵育24小时。本实验结果表明，VCR不仅能诱导DNA损伤，显著增加微核频率和凋亡细胞比例，并呈剂量反应关系降低核分裂指数（NDI），还能产生核质桥（NPBs，一种DNA错配修复和/或端粒末端融合的生物标志物）和核芽（NBUDs，一种消除扩增DNA和/或DNA修复复合物的生物标志物）。此外，VCR可提高人淋巴细胞的TCR基因突变频率（Mf-TCR）。这些参数（平均尾长、平均尾矩、微核频率、微核化频率和Mf-TCR）之间存在良好的相关性。本研究结果支持了我们之前针对职业性接触VCR的工人所做调查的结果，并在体外不同遗传终点确定了VCR的遗传毒性。
