Nitrophenols isolated from diesel exhaust particles promote the growth of MCF-7 breast adenocarcinoma cells
Nitrophenols isolated from diesel exhaust particles promote the growth of MCF-7 breast adenocarcinoma cells
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DOI：
10.1016/j.taap.2008.02.027
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发表时间：
2008-08-01
影响因子：
3.8
通讯作者：
Taya, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Furuta, Chie;Suzuki, Akira K.;Taya, Kazuyoshi
柴油机排气颗粒（DEP）会导致许多不利的健康问题，有报告表明，男性和女性因接触汽油和汽车尾气而患乳腺癌的风险增加。然而，DEP包括大量的化合物，并且负责这些作用的具体化合物尚不清楚。最近，我们从DEPs中分离出两种硝基酚类化合物：3-甲基-4-硝基苯酚（4-nitro-m-cresol; PNMC）和4-硝基-3-苯基苯酚（PNMPP），并发现它们具有雌激素和抗雄激素活性。在这里，我们试图澄清这两个硝基酚参与促进MCF-7乳腺癌细胞系的生长。首先，采用彗星试验检测PNMC和PNMPP对CHO细胞的遗传毒性。在所有试验剂量下，PNMC和PNMPP均显示阴性遗传毒性，表明它们没有肿瘤引发活性。接下来，使用雌激素响应性乳腺癌细胞系MCF-7来评估细胞增殖。PNMC、PNMPP和雌二醇-17 β刺激MCF-7细胞增殖，抗雌激素4-羟基他莫昔芬和ICI 182，780抑制增殖。为了进一步研究通过雌激素受体的转录活性，用受体基因转染MCF-7细胞，该受体基因允许在雌激素调节元件的控制下表达荧光素酶。PNMC和PNMPP在亚微摩尔浓度下以剂量依赖性方式诱导荧光素酶活性。ICI 182，780抑制PNMC和PNMPP诱导的荧光素酶活性。这些结果清楚地表明，PNMC和PNMPP不显示遗传毒性，但作为肿瘤促进剂在雌激素受体α-占主导地位的乳腺癌细胞系。(C)2008年爱思唯尔公司All rights reserved.
Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of breast cancer in men and women through exposure to gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recently isolated two nitrophenols from DEPs-3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro3-phenylphenol (PNMPP)-and showed that they had estrogenic and anti-androgenic activities. Here, we tried to clarify the involvement of these two nitrophenols in promoting the growth of the MCF-7 breast cancer cell line. First, comet assay was used to detect the genotoxicity of PNMC and PNMPP in a CHO cell line. At all doses tested, PNMC and PNMPP showed negative genotoxicity, indicating that they had no tumor initiating activity. Next, the estrogen-responsive breast cancer cell line MCF-7 was used to assess cell proliferation. Proliferation of MCF-7 cells was stimulated by PNMC, PNMPP, and estradiol-17 beta and the anti-estrogens 4-hydroxytamoxifen and ICI 182,780 inhibited the proliferation. To further investigate transcriptional activity through the estrogen receptor, MCF-7 cells were transfected with a receptor gene that allowed expression of luciferase enzyme under the control of the estrogen regulatory element. PNMC and PNMPP induced luciferase activity in a dose-dependent manner at submicromolar concentrations. ICI 182,780 inhibited the luciferase activity induced by PNMC and PNMPP. These results clearly indicate that PNMC and PNMPP do not show genotoxicity but act as tumor promoters in an estrogen receptor a-predominant breast cancer cell line. (C) 2008 Elsevier Inc. All rights reserved.