Farasani A, Darbre P D
School of Biological Sciences, University of Reading, Reading RG6 6UB, UK.
School of Biological Sciences, University of Reading, Reading RG6 6UB, UK.
J Inorg Biochem. 2015 Nov;152:186-9. doi: 10.1016/j.jinorgbio.2015.08.003. Epub 2015 Aug 15.
Use of underarm aluminium (Al)-based antiperspirant salts may be a contributory factor in breast cancer development. At the 10th Keele meeting, Al was reported to cause anchorage-independent growth and double strand DNA breaks in MCF10A immortalised non-transformed human breast epithelial cells. We now report that exposure of MCF10A cells to Al chloride or Al chlorohydrate also compromised DNA repair systems. Long-term (19-21 weeks) exposure to Al chloride or Al chlorohydrate at a 10(-4) M concentration resulted in reduced levels of BRCA1 mRNA as determined by real-time RT-PCR and BRCA1 protein as determined by Western immunoblotting. Reduced levels of mRNA for other DNA repair genes (BRCA2, CHK1, CHK2, Rad51, ATR) were also observed using real-time RT-PCR. Loss of BRCA1 or BRCA2 gene function has long been associated with inherited susceptibility to breast cancer but these results suggest that exposure to aluminium-based antiperspirant salts may also reduce levels of these key components of DNA repair in breast epithelial cells. If Al can not only damage DNA but also compromise DNA repair systems, then there is the potential for Al to impact on breast carcinogenesis.
使用腋下铝基止汗盐可能是乳腺癌发展的一个促成因素。在第十届基尔会议上，有报告称铝会导致MCF10A永生化非转化人乳腺上皮细胞出现不依赖贴壁生长和双链DNA断裂。我们现在报告，将MCF10A细胞暴露于氯化铝或碱式氯化铝也会损害DNA修复系统。通过实时逆转录聚合酶链反应（RT-PCR）测定，长期（19 - 21周）暴露于浓度为10⁻⁴ M的氯化铝或碱式氯化铝会导致BRCA1 mRNA水平降低，通过蛋白质免疫印迹法测定，BRCA1蛋白水平也降低。使用实时RT-PCR还观察到其他DNA修复基因（BRCA2、CHK1、CHK2、Rad51、ATR）的mRNA水平降低。长期以来，BRCA1或BRCA2基因功能的丧失一直与遗传性乳腺癌易感性相关，但这些结果表明，暴露于铝基止汗盐也可能降低乳腺上皮细胞中这些DNA修复关键成分的水平。如果铝不仅能损伤DNA，还会损害DNA修复系统，那么铝就有可能影响乳腺癌的发生。
