School of Biological Sciences, University of Reading, Reading, RG66UB, UK.
J Appl Toxicol. 2013 May;33(5):390-8. doi: 10.1002/jat.2850. Epub 2013 Jan 31.
The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually.
对羟基苯甲酸酯（parabens）作为消费品中的防腐剂被广泛使用，具有雌激素活性，并已在人体乳腺组织中被检测到。这引起了人们对其在人类乳腺癌发展中潜在作用的关注。在本文中，我们研究了 MCF-7 人乳腺癌细胞在单独或联合接触最近在 160 个人体乳腺组织样本中测量到的浓度的五种对羟基苯甲酸酯时，其增殖可以增加到何种程度。确定五种对羟基苯甲酸酯刺激 MCF-7 细胞增殖的无观察效应浓度（NOEC）、最低观察效应浓度（LOEC）、EC50 和 EC100 值表明，在至少 160 个人体乳腺组织样本中，有 43/160（27%）个样本中含有一种或多种对羟基苯甲酸酯的浓度≥LOEC，64/160（40%）>NOEC。五种对羟基苯甲酸酯联合使用时，其浓度可以低至组织中测量到的第 50（百分位）值（中位数），仍能增加 MCF-7 细胞的增殖。对于在 ER+PR+原发性癌症部位采集的 22 个组织样本，有 12 个样本中含有足够浓度的一种或多种对羟基苯甲酸酯，足以刺激 MCF-7 细胞的增殖。这表明，对羟基苯甲酸酯无论是单独存在还是联合存在，都以足以刺激 MCF-7 细胞在体外增殖的浓度存在于人体乳腺组织中，并且应该根据所有五种对羟基苯甲酸酯而不是单个对羟基苯甲酸酯来评估对羟基苯甲酸酯在人乳腺组织中的存在的功能后果。
