Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
J Toxicol Environ Health A. 2011;74(15-16):1030-9. doi: 10.1080/15287394.2011.582282.
Two model chromium (Cr) compounds, one hexavalent (sodium chromate) and one trivalent (chromium chloride), were investigated in a human lymphoblastoid cell line (TK6) to increase our knowledge regarding Cr-induced genotoxicity mechanisms. Both selected compounds were genotoxic using the comet assay, although the percentage of DNA in tail obtained after treatment with Cr(VI) was significantly higher than that obtained with Cr(III), at the higher concentrations tested. To determine the nature of the induced damage, enzymes recognizing oxidized bases were used. Treatments with formamidopyrimidine (FPG) and endonuclease III (EndoIII) displayed a greater degree of DNA damage, indicating that the induction of oxidized bases accounts for an important proportion of the damage induced by Cr compounds. In addition, the kinetic repair studies showed that generated DNA damage is removed in approximately 8 h, with the damage induced by Cr(III) being removed/repaired more rapidly than damage produced by Cr(VI). To detect Cr interferences with the repair process, a post-treatment was applied after exposure to 2 Gy gamma radiation. Post-treatment significantly delayed the repair kinetics of DNA damage induced by radiation. This interference effect induced by Cr(VI) was more pronounced. In conclusion, evidence indicates that a high proportion of the Cr-induced DNA damage is correlated with oxidative damage, and that both Cr compounds interfere with repair mechanisms involved in repair of DNA damage induced by gamma radiation.
两种模式铬（Cr）化合物，一种六价（铬酸钠）和一种三价（氯化铬），在人类淋巴母细胞系（TK6）中进行了研究，以增加我们对 Cr 诱导遗传毒性机制的认识。彗星试验显示两种选定的化合物均具有遗传毒性，但 Cr(VI)处理后获得的 DNA 在尾部的百分比明显高于 Cr(III)，在测试的较高浓度下更是如此。为了确定诱导损伤的性质，使用识别氧化碱基的酶。使用 5-甲酰基嘧啶（FPG）和内切酶 III（EndoIII）处理显示出更高程度的 DNA 损伤，表明氧化碱基的诱导占 Cr 化合物诱导损伤的重要比例。此外，动力学修复研究表明，生成的 DNA 损伤在大约 8 小时内被清除，Cr(III)诱导的损伤比 Cr(VI)产生的损伤被清除/修复得更快。为了检测 Cr 对修复过程的干扰，在暴露于 2 Gy 伽马射线后进行了后处理。后处理显著延迟了由辐射诱导的 DNA 损伤的修复动力学。Cr(VI)引起的这种干扰效应更为明显。总之，有证据表明，高比例的 Cr 诱导的 DNA 损伤与氧化损伤相关，并且两种 Cr 化合物均干扰涉及修复伽马辐射诱导的 DNA 损伤的修复机制。
