Mechanism of carcinogenesis in female reproductive organs induced by environmental estrogens

环境雌激素诱发女性生殖器官癌变的机制

基本信息

批准号：
17590511
负责人：
MURATA Mariko
金额：
$ 2.24万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Chemical pollutant has some potential to alter estrogenic responses, and therefore its presence in the environment may be of concern for reproductive health. It may be involved with the increased incidence rates of breast cancer and endometrial cancer in most countries worldwide. Carcinogenesis is a multistage process, consisting of initiation, promotion, and progression phases. The tumor-initiation process starts DNA damage, leading to irreversible gene alteration. The tumor-promotion process requires sustained exposure to agents that stimulate the growth.Salsolinol (Sal) is an endogenous metabolite of alcohol, generated by condensation reaction of dopamine with acetaldehyde, a major ethanol metabolite. Sal induced DNA damage including 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in the presence of Cu(II) or Fe(III)EDTA. Catalase and metal-specific chelators inhibited SAL-induced DNA damage, suggesting the involvement of H2O2 and transition metals. SAL induced proliferation in estrogen-sensitive breast cancer MCF-7 cells, and the proliferation was inhibited by 4-hydroxytamoxifen, suggesting the involvement of estrogen receptor. In addition, SAL increased estrogen-independent mammary epithelial MCF-10A cells, and the proliferation was inhibited by an antioxidant N-acetylcysteine, suggesting that ROS may participate in proliferation of MCF-10A cells via EGFR activation. We demonstrated that SAL induces oxidative DNA damage and mammary cell proliferation, which may play important roles in tumor initiation and promotion of multistage breast cancer development in relation to alcohol drinking. Furthermore, we have revealed that plant polyphenol procyanidin B2(Free Radic. Biol. Med. 39, 1041-1049, 2005), air pollutant 3-nitrobenzanthrone (Free Radic. Biol. Med. 40, 1242-1249, 2006), and hair dye components ortho-phenylenediamine (Mutat. Res. 607, 184-191, 2006) have the DNA damaging abilities.

化学污染物具有改变雌激素反应的潜力，因此其在环境中的存在可能会引起生殖健康。它可能与全球大多数国家的乳腺癌和子宫内膜癌的发病率提高有关。致癌过程是一个多阶段过程，由起始，促进和进展阶段组成。肿瘤发射过程开始DNA损伤，导致不可逆的基因改变。肿瘤促进过程需要持续暴露于刺激生长的药物中。Salsolinol（SAL）是一种内源性代谢物，是由多巴胺与主要乙醇代谢物乙醛醛的凝结反应产生的。 SAL诱导的DNA损伤，包括8-氧-7,8-二氢-2'-脱氧鸟苷，在Cu（II）或Fe（III）EDTA的存在下形成。过氧化氢酶和金属特异性螯合剂抑制了SAL诱导的DNA损伤，表明H2O2和过渡金属的参与。 SAL诱导雌激素敏感的乳腺癌MCF-7细胞的增殖，4-羟基氧莫昔芬抑制了增殖，这表明雌激素受体的参与。此外，SAL增加了雌激素非依赖性的乳腺上皮MCF-10A细胞，并且抗氧化剂N-乙酰半胱氨酸抑制了增殖，这表明ROS可以通过EGFR激活参与MCF-10A细胞的增殖。我们证明了SAL诱导氧化性DNA损伤和乳腺细胞增殖，这可能在肿瘤起始和促进多阶段乳腺癌发育方面起着重要作用，与饮酒有关。此外，我们已经透露植物多酚procyanidin B2（自由放射性生物学39，1041-1049，2005），空气污染物3-硝基苯甲酮（自由radic。Biol。Biol。40，40，1242-1249，2006，2006）和Dye Components and dye components or they orthoiamniamneymine（intheyamneediam）。 2006）具有DNA损害能力。

项目成果

期刊论文数量（40）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

iNOS-dependent DNA damage via NF-kB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel

感染 Opisthorchis viverrini 的仓鼠中通过 NF-kB 表达造成的 iNOS 依赖性 DNA 损伤及其抗蠕虫药物吡喹酮的抑制

DOI：
发表时间：
2006
期刊：
Int. J. Cancer 119・5
影响因子：
0
作者：
Pinlaor;S.;Hiraku;Y.;Yongvanit;P.;Tada-Oikawa;S.;Ma;N.;Pinlaor;P.;Sithithaworn;P.;Sripa;B.;Murata M.;Oikawa;S.;Kawanishi S.
通讯作者：
Kawanishi S.

DNA障害マーカー

DNA 紊乱标记