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重金属对乳腺癌进展的影响。

Heavy metals effect on breast cancer progression.

作者信息

Romaniuk А, Lyndin M, Sikora V, Lyndina Y, Romaniuk S, Sikora K

机构信息

Department of pathology, Sumy State University, st. Privokzalnaya, 31, Sumy, Postal code 40022 Ukraine.

Department of normal anatomy, Sumy State University, Sumy, Ukraine.

出版信息

J Occup Med Toxicol. 2017 Nov 28;12:32. doi: 10.1186/s12995-017-0178-1. eCollection 2017.

Abstract

BACKGROUND

Breast cancer is the most frequent localization of malignant process in American women and women of European countries. To date it is not possible to control the morbidity growth due to lack of effective ways of primary prevention. Comparing the incidence of breast cancer in developed countries with the countries of Asia and Africa, there is the fact of population predominance lesion in more urbanized countries. This suggests that the environment along with other factors, occupies a significant place in the initiation and progression of breast neoplasia. The impressive rates of industrial development led to the pollution of soil, surface water and, as a consequence, food by heavy metal salts.The purposes of this paper are as follows: the chemical composition determination of neoplastic breast tissue, evaluation of the DNA methylation level, study of prognostic-important receptors expression in the breast cancer cells, establishing linkages between all the derived indicators.

METHODS

In our study we used the following methods: studying of the chemical composition of breast cancer tissue by atomic absorption spectrophotometry and energy-dispersion spectrometer; іmmunohistochemical study of ER, PR, HER2/neu, p53, Ki-67, E-cadherin and MGMT receptors; DNA extraction and investigation by oscillating infrared spectroscopy method.

RESULTS

The total amount of heavy metals in breast cancer tissue ranged from 51.21 × 10 to 84.86 × 10 μg/kg. We have got the following results: the growth of heavy metals in neoplastic tissue is accompanied with the increase of HER2/neu, p53, Ki-67, MGMT expression and decrease of ER and PR expression. The increment of pathological DNA methylation is accompanied with the increasing amount of heavy metals in tumor tissue.

CONCLUSIONS

Heavy metals through different pathogenetic links stimulate the progression of breast cancer and reduce its sensitivity to treatment. DNA of tumor tissue has a different level of methylation which changes with the amount of heavy metals in cancer cells. This is displayed on the synthesis of prognostically important receptors in neoplastic tissue.

摘要

背景

乳腺癌是美国女性和欧洲国家女性恶性肿瘤最常见的发病部位。由于缺乏有效的一级预防方法,目前无法控制发病率的增长。比较发达国家与亚洲和非洲国家的乳腺癌发病率,存在城市化程度较高国家的人群发病占优势的情况。这表明环境与其他因素在乳腺肿瘤的发生和发展中占据重要地位。工业发展的惊人速度导致土壤、地表水以及随之而来的食物被重金属盐污染。本文的目的如下:确定肿瘤性乳腺组织的化学成分,评估DNA甲基化水平,研究乳腺癌细胞中具有预后重要性的受体表达情况,建立所有所得指标之间的联系。

方法

在我们的研究中,我们使用了以下方法:通过原子吸收分光光度法和能量色散光谱仪研究乳腺癌组织的化学成分;对雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2/neu)、p53、Ki-67、E-钙黏蛋白和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)受体进行免疫组织化学研究;通过振荡红外光谱法进行DNA提取和研究。

结果

乳腺癌组织中重金属总量在51.21×10至84.86×10μg/kg之间。我们得到了以下结果:肿瘤组织中重金属含量的增加伴随着HER2/neu、p53、Ki-67、MGMT表达的增加以及ER和PR表达的降低。病理性DNA甲基化的增加伴随着肿瘤组织中重金属含量的增加。

结论

重金属通过不同的致病途径刺激乳腺癌的进展并降低其对治疗的敏感性。肿瘤组织的DNA具有不同水平的甲基化,其随癌细胞中重金属含量的变化而变化。这在肿瘤组织中具有预后重要性的受体合成中得以体现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b60/5704424/53b7221ab063/12995_2017_178_Fig1_HTML.jpg

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