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对苯二甲酸酯可使 MCF-10A 永生化、非转化的人乳腺上皮细胞悬浮生长。

Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells.

机构信息

Biomedical Sciences Section, School of Biological Sciences, University of Reading, Reading, RG6 6UB, UK.

出版信息

J Appl Toxicol. 2013 May;33(5):378-82. doi: 10.1002/jat.2753. Epub 2012 Jun 29.

DOI:10.1002/jat.2753
PMID:22744862
Abstract

Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P < 0.05 in each case) and an increased average colony size (P < 0.001 in each case). Dose-responses showed that concentrations as low as 10(-6) M methylparaben, 10(-7) M n-propylparaben and 10(-7) M n-butylparaben could increase colony numbers (P = 0.016, P = 0.010, P = 0.008, respectively): comparison with a recent measurement of paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis.

摘要

对羟基苯甲酸酯(对羟基苯甲酸的烷基酯)被广泛用作消费品中的防腐剂,并且已经在几种人体组织中测量到完整的酯类。人们对防腐剂与乳腺癌之间可能存在联系表示担忧,但机制研究主要集中在其雌激素活性上,很少关注任何致癌特性。在本研究中,我们报告对羟基苯甲酸酯可以诱导 MCF-10A 永生化但未转化的人乳腺上皮细胞的无锚定依赖性生长,这一特性与转化密切相关,也是体内肿瘤生长的预测因子。在半固体甲基纤维素悬浮培养中,MCF-10A 细胞产生的菌落很少且体积很小,但添加 5×10(-4) M 甲基对羟基苯甲酸酯、10(-5) M 正丙基对羟基苯甲酸酯或 10(-5) M 正丁基对羟基苯甲酸酯可导致每皿菌落数量增加(每种情况下 P<0.05),并且平均菌落尺寸增加(每种情况下 P<0.001)。剂量反应表明,浓度低至 10(-6) M 甲基对羟基苯甲酸酯、10(-7) M 正丙基对羟基苯甲酸酯和 10(-7) M 正丁基对羟基苯甲酸酯即可增加菌落数量(P=0.016、P=0.010、P=0.008):与 Barr 等人最近对 40 例乳房切除术患者乳腺组织样本中对羟基苯甲酸酯浓度的测量(2012)进行比较,22/40 例患者在原发性肿瘤部位至少有一种对羟基苯甲酸酯的浓度达到或高于这些浓度。据我们所知,这是第一项报道对羟基苯甲酸酯可在体外诱导人乳腺上皮细胞发生转化表型的研究,现在有理由进一步研究对羟基苯甲酸酯与乳腺癌发生之间的潜在联系。

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