Aluminium, antiperspirants and breast cancer
Aluminium, antiperspirants and breast cancer
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DOI：
10.1016/j.jinorgbio.2005.06.001
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发表时间：
2005-09-01
影响因子：
3.9
通讯作者：
Darbre, PD
中科院分区：
文献类型：
--
作者：
Darbre, PD
铝盐被用作腋下化妆品中的活性止汗剂，但广泛、长期和日益增加的使用的影响仍然未知，特别是与局部应用领域的乳房有关的影响。临床研究显示，乳腺外象限的乳腺癌发病率不成比例地高，同时报告了乳腺外象限的基因组不稳定性，为局部应用的化妆品化学品在乳腺癌发展中的作用提供了支持性证据。已知铝具有遗传毒性特征，能够引起DNA改变和表观遗传效应，如果这种效应发生在乳腺细胞中，则这与乳腺癌的潜在作用一致。雌激素在乳腺癌中是一种公认的影响，其作用依赖于细胞内受体，这些受体作为配体激活的锌指转录因子发挥作用，这表明铝可能存在一个干扰点。本文报道的结果表明，氯化铝或氯化铝水合物形式的铝可以干扰MCF 7人乳腺癌细胞的雌激素受体的功能，无论是在配体结合方面，还是在雌激素调节的报告基因表达方面。这将铝添加到越来越多的能够干扰雌激素作用的金属列表中，并称为金属I雌激素。现在需要进一步的研究来确定这种作用的分子基础，铝暴露的长期影响以及铝是否会导致乳腺细胞中其他信号通路的畸变。鉴于人群广泛暴露于止汗剂，重要的是确定乳房局部区域的皮肤吸收，以及长期低水平吸收是否会在乳腺癌发病率增加中发挥作用。(c)2005年爱思唯尔公司All rights reserved.
Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metal I oestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer. (c) 2005 Elsevier Inc. All rights reserved.