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首页> 外文期刊>Journal of applied toxicology >Effect of sulphur mustard on human skin cell lines with differential agent sensitivity.
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Effect of sulphur mustard on human skin cell lines with differential agent sensitivity.

机译：硫芥菜对人皮肤细胞系的影响具有不同的药物敏感性。

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摘要

The ability of sulphur mustard (HD) to induce DNA damage places limits on the efficacy of approaches aimed at protecting human cells from the cytotoxic effects of HD using a variety of protective agents such as thiol-containing esters and protease inhibitors. In the present study, potential alternative strategies were investigated by examining the differential effects of HD on G361, SVK14, HaCaT and NCTC 2544 human skin cells. The G361 cell line was more resistant to the cytotoxic effects of HD than the NCTC, HaCaT and SVK14 cell lines at HD doses of >3 and <100 microM HD as determined by the MTT assay. At 72 h after exposure to 60 microM HD there was up to an 8.8-fold difference (P < 0.0001) between G361 and SVK14 cell culture viability. Buthionine sulphoximine (BSO) pretreatment increased the sensitivity of all four cell lines to HD. A substantial proportion of the resistance of G361 cells to HD was attributable to BSO-mediated effects on antioxidant-mediated metabolism, although G361 cultures still retained a high degree of viability at 30 microM HD following BSO pretreatment. Cell cycle analysis confirmed that SVK14 cells were relatively more sensitive to HD, as shown by the 2.1-fold reduction (P < 0.0001) in the percentage of cells in G0/G1 phase 24 h after HD exposure compared with control cultures. This compared well with a 1.2-fold increase (P < 0.05) in the percentage of G361 cells in G0/G1 phase following HD exposure, suggesting the existence of a more efficient G0/G1 checkpoint control mechanism in this cell line. Manipulation of the cell cycle using various modulating agents did not increase the resistance of cell lines to the cytotoxic effects of HD.
机译：硫芥子（HD）诱导DNA损伤的能力限制了旨在使用多种保护剂（例如含硫醇的酯和蛋白酶抑制剂）保护人类细胞免受HD的细胞毒作用的方法的功效。在本研究中，通过检查HD对G361，SVK14，HaCaT和NCTC 2544人皮肤细胞的差异作用，研究了潜在的替代策略。如通过MTT测定法所确定的，在> 3和<100 microM HD的HD剂量下，G361细胞系比NCTC，HaCaT和SVK14细胞系对HD的细胞毒性作用更具抗性。暴露于60 microM HD后72小时，G361和SVK14细胞培养活力之间的差异高达8.8倍（P <0.0001）。丁硫氨酸亚砜（BSO）预处理增加了所有四个细胞系对HD的敏感性。 G361细胞对HD的抗性的很大一部分归因于BSO介导的抗氧化剂介导的代谢作用，尽管在BSO预处理后G361培养物在30 microM HD下仍保持了高度的活力。细胞周期分析证实了SVK14细胞对HD相对更敏感，HD暴露后24 h与对照培养相比，G0 / G1期的细胞百分比降低了2.1倍（P <0.0001），这表明。这与HD暴露后G0 / G1期中G361细胞的百分数增加了1.2倍（P <0.05）相比，表明该细胞系中存在更有效的G0 / G1检查点控制机制。使用各种调节剂操纵细胞周期并没有增加细胞系对HD细胞毒性作用的抗性。

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