Viau C M, Guecheva Temenouga N, Sousa F G, Pungartnik C, Brendel M, Saffi J, Henriques João Antonio Pêgas
Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, Brazil.
Arch Toxicol. 2009 Aug;83(8):769-75. doi: 10.1007/s00204-009-0409-z. Epub 2009 Mar 3.
In order to clarify the molecular mechanisms of Sn(2+) genotoxicity, we evaluated the induction of strand breaks, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (Endo III) sensitive sites, and the interference with the repair of methyl methane sulfonate (MMS)-caused DNA damage in V79 Chinese hamster lung fibroblasts exposed to stannous chloride by comet assay. A concentration-related increase in the DNA damage induced by 2 h SnCl(2) treatment at a concentration range of 50-1,000 microM was observed (r = 0.993; P < 0.01). Significantly elevated DNA migration in relation to the control level was detected at doses 100, 500 and 1,000 microM in normal alkaline and at doses 500 and 1,000 microM in modified (with Fpg and Endo III) comet assay. Although 50 microM SnCl(2) concentration did not increase significantly the DNA migration by itself in comet assay, it was capable to inhibit the repair of MMS-induced DNA damage during the post-treatment period of 24 h. Our results demonstrate the genotoxic and comutagenic effects of stannous chloride in V79 cells. The inhibitory effect of Sn(2+) on repair of MMS-induced DNA damage suggests that this metal can also interfere in DNA repair systems thus contributing to increased mutation by shifting the balance from error-free to error-prone repair processes.
为了阐明Sn(2+)的遗传毒性分子机制，我们通过彗星试验评估了链断裂、甲酰胺嘧啶DNA糖基化酶（Fpg）和核酸内切酶III（Endo III）敏感位点的诱导情况，以及在暴露于氯化亚锡的V79中国仓鼠肺成纤维细胞中对甲磺酸甲酯（MMS）引起的DNA损伤修复的干扰。观察到在50-1000 microM浓度范围内，2小时SnCl(2)处理诱导的DNA损伤呈浓度相关增加（r = 0.993；P < 0.01）。在正常碱性彗星试验中，100、500和1000 microM剂量时检测到DNA迁移相对于对照水平显著升高，在改良（添加Fpg和Endo III）彗星试验中，500和1000 microM剂量时也有显著升高。尽管50 microM SnCl(2)浓度本身在彗星试验中未显著增加DNA迁移，但它能够在24小时的后处理期抑制MMS诱导的DNA损伤修复。我们的结果证明了氯化亚锡在V79细胞中的遗传毒性和共诱变作用。Sn(2+)对MMS诱导的DNA损伤修复的抑制作用表明，这种金属还可干扰DNA修复系统，从而通过将平衡从无差错修复过程转向易错修复过程导致突变增加。
