Ivancsits Sabine, Pilger Alexander, Diem Elisabeth, Schaffer Andreas, Rüdiger Hugo W
Division of Occupational Medicine, University Hospital/AKH, University of Vienna, Waehringer Guertel 18-20, Austria.
Mutat Res. 2002 Aug 26;519(1-2):25-35. doi: 10.1016/s1383-5718(02)00138-9.
To study possible genotoxic effects of occupational exposure to vanadium pentoxide, we determined DNA strand breaks (with alkaline comet assay), 8-hydroxy-2'deoxyguanosine (8-OHdG) and the frequency of sister chromatid exchange (SCE) in whole blood leukocytes or lymphocytes of 49 male workers employed in a vanadium factory in comparison to 12 non-exposed controls. In addition, vanadate has been tested in vitro to induce DNA strand breaks in whole blood cells, isolated lymphocytes and cultured human fibroblasts of healthy donors at concentrations comparable to the observed levels of vanadium in vivo. To investigate the impact of vanadate on the repair of damaged DNA, co-exposure to UV or bleomycin was used in fibroblasts, and DNA migration in the alkaline and neutral comet assay was determined. Although, exposed workers showed a significant vanadium uptake (serum: median 5.38microg/l, range 2.18-46.35microg/l) no increase in cytogenetic effects or oxidative DNA damage in leukocytes could be demonstrated. This was consistent with the observation that in vitro exposure of whole blood leukocytes and lymphocytes to vanadate caused no significant changes in DNA strand breaks below concentrations of 1microM (50microg/l). In contrast, vanadate clearly induced DNA fragmentation in cultured fibroblasts at relevant concentrations. Combined exposure of fibroblasts to vanadate/UV or vanadate/bleomycin resulted in non-repairable DNA double strand breaks (DSBs) as seen in the neutral comet assay. We conclude that exposure of human fibroblasts to vanadate effectively causes DNA strand breaks, and co-exposure of cells to other genotoxic agents may result in persistent DNA damage.
为研究职业性接触五氧化二钒可能产生的遗传毒性效应，我们测定了49名钒厂男性工人全血白细胞或淋巴细胞中的DNA链断裂（采用碱性彗星试验）、8-羟基-2'-脱氧鸟苷（8-OHdG）以及姐妹染色单体交换（SCE）频率，并与12名未接触者进行对照。此外，还在体外对钒酸盐进行了测试，以观察其在与体内观察到的钒水平相当的浓度下，对健康供体的全血细胞、分离的淋巴细胞和培养的人成纤维细胞诱导DNA链断裂的情况。为研究钒酸盐对受损DNA修复的影响，在成纤维细胞中采用钒酸盐与紫外线或博来霉素共同暴露，并通过碱性和中性彗星试验测定DNA迁移情况。尽管接触工人显示出明显的钒摄取（血清：中位数5.38μg/l，范围2.18 - 46.35μg/l），但未发现白细胞的细胞遗传学效应或氧化性DNA损伤增加。这与以下观察结果一致：体外将全血白细胞和淋巴细胞暴露于钒酸盐，在浓度低于1μM（50μg/l）时，DNA链断裂无显著变化。相反，在相关浓度下，钒酸盐明显诱导培养的成纤维细胞中的DNA片段化。如中性彗星试验所示，成纤维细胞同时暴露于钒酸盐/紫外线或钒酸盐/博来霉素会导致不可修复的DNA双链断裂（DSB）。我们得出结论，人成纤维细胞暴露于钒酸盐会有效导致DNA链断裂，细胞与其他遗传毒性剂共同暴露可能导致持续性DNA损伤。
