Wise Sandra S, Schuler Julie H C, Katsifis Spiros P, Wise John Pierce
Center for Integrated and Applied Environmental Toxicology, Wise Laboratory of Environmental and Genetic Toxicology, Bioscience Research Institute, University of Southern Maine, Portland, Maine 04104-9300, USA.
Environ Mol Mutagen. 2003;42(4):274-8. doi: 10.1002/em.10203.
Hexavalent chromium (Cr(VI)) compounds are widely accepted as human lung carcinogens. However, there have been few investigations of the genotoxicity of Cr(VI) in human lung cells. Moreover, our knowledge of the effects of Cr(VI) in human lung cells is further limited because the available data generally focus on the effects of only lead chromate (PbCrO(4)) and sodium chromate (Na(2)CrO(4)). To fully understand these carcinogenic compounds, the genotoxic effects to its target cells need to be evaluated for additional Cr(VI) salts. Accordingly, we investigated the cytotoxicity and clastogenicity of barium chromate (BC) in a human lung cell culture model (WTHBF-6 cells). We found that BC induced concentration-dependent cytotoxicity in WTHBF-6 cells, with relative survival of 88%, 74%, 67%, 12%, 3%, and 0.1% after exposure to 0.01, 0.05, 0.1, 0.5, 1, and 5 microg/cm(2) BC, respectively. Similarly, the amount of chromosomal damage also increased with concentration after a 24-h exposure. Specifically, 0.01, 0.05, 0.1, and 0.5 microg/cm(2) BaCrO(4) damaged 5%, 9%, 22%, and 49% of metaphase cells, with the total damage reaching 5, 10, 28, and 65 aberrations per 100 metaphases, respectively. Concentrations of 1 and 5 microg/cm(2) BC induced a profound cell cycle delay, and no metaphases were observed. The spectrum of damage included chromatid and chromosome-type lesions consistent with mechanistic events associated with the activation of oncogenes and inactivation of tumor suppressor genes. Overall the data indicate that BC is cytotoxic and genotoxic to human lung cells.
六价铬(Cr(VI))化合物被广泛认为是人类肺癌致癌物。然而,关于Cr(VI)对人肺细胞遗传毒性的研究却很少。此外,我们对Cr(VI)在人肺细胞中作用的了解进一步受限,因为现有数据通常仅关注铬酸铅(PbCrO(4))和铬酸钠(Na(2)CrO(4))的作用。为了全面了解这些致癌化合物,则需要评估其他Cr(VI)盐对其靶细胞的遗传毒性作用。因此,我们在人肺细胞培养模型(WTHBF - 6细胞)中研究了铬酸钡(BC)的细胞毒性和致断裂性。我们发现BC在WTHBF - 6细胞中诱导浓度依赖性细胞毒性,暴露于0.01、0.05、0.1、0.5、1和5μg/cm(2) BC后,相对存活率分别为88%、74%、67%、12%、3%和0.1%。同样,24小时暴露后,染色体损伤数量也随浓度增加而增加。具体而言,0.01、0.05、0.1和0.5μg/cm(2) BaCrO(4)分别使5%、9%、22%和49%的中期细胞受损,每100个中期细胞的总损伤分别达到5、10、28和65个畸变。1和5μg/cm(2) BC的浓度诱导了严重的细胞周期延迟,未观察到中期细胞。损伤谱包括染色单体和染色体类型的损伤,这与与癌基因激活和肿瘤抑制基因失活相关的机制事件一致。总体而言,数据表明BC对人肺细胞具有细胞毒性和遗传毒性。