Division of Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
J Appl Toxicol. 2012 Mar;32(3):233-43. doi: 10.1002/jat.1793. Epub 2012 Jan 6.
Aluminium salts used as antiperspirants have been incriminated as contributing to breast cancer incidence in Western societies. To date, very little or no epidemiological or experimental data confirm or infirm this hypothesis. We report here that in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminium chloride (AlCl(3) ) concentrations of 10-300 µ m, i.e. up to 100 000-fold lower than those found in antiperspirants, and in the range of those recently measured in the human breast, results in loss of contact inhibition and anchorage-independent growth. These effects were preceded by an increase of DNA synthesis, DNA double strand breaks (DSBs), and senescence in proliferating cultures. AlCl(3) also induced DSBs and senescence in proliferating primary human mammary epithelial cells. In contrast, it had no similar effects on human keratinocytes or fibroblasts, and was not detectably mutagenic in bacteria. MCF-10A cells morphologically transformed by long-term exposure to AlCl(3) display strong upregulation of the p53/p21(Waf1) pathway, a key mediator of growth arrest and senescence. These results suggest that aluminium is not generically mutagenic, but similar to an activated oncogene, it induces proliferation stress, DSBs and senescence in normal mammary epithelial cells; and that long-term exposure to AlCl(3) generates and selects for cells able to bypass p53/p21(Waf1) -mediated cellular senescence. Our observations do not formally identify aluminium as a breast carcinogen, but challenge the safety ascribed to its widespread use in underarm cosmetics.
铝盐被用作止汗剂，已被指认为导致西方社会乳腺癌发病率上升的原因之一。迄今为止，几乎没有或没有流行病学或实验数据证实或证实了这一假说。我们在这里报告，在 MCF-10A 人乳腺上皮细胞，一种成熟的正常人类乳腺上皮细胞模型中，长期暴露于氯化铝（AlCl(3)）浓度为 10-300µm，即比止汗剂中的浓度低 100000 倍，与最近在人类乳房中测量到的浓度相当，导致接触抑制丧失和锚定独立生长。这些效应之前是 DNA 合成、DNA 双链断裂（DSBs）和增殖培养物中的衰老增加。AlCl(3)也在增殖的原代人乳腺上皮细胞中诱导 DSBs 和衰老。相比之下，它对人角质形成细胞或成纤维细胞没有类似的影响，并且在细菌中没有可检测的致突变性。长期暴露于 AlCl(3)的 MCF-10A 细胞形态转化，显示出 p53/p21(Waf1)途径的强烈上调，这是生长抑制和衰老的关键介质。这些结果表明，铝不是普遍的致突变剂，但类似于激活的致癌基因，它在正常乳腺上皮细胞中诱导增殖应激、DSBs 和衰老；并且长期暴露于 AlCl(3)会产生和选择能够绕过 p53/p21(Waf1)介导的细胞衰老的细胞。我们的观察结果并没有正式将铝确定为乳腺癌致癌物，但对其在腋下化妆品中的广泛使用所赋予的安全性提出了挑战。
