乳腺癌、卵巢癌和子宫癌是最常见的女性恶性肿瘤之一。它们被怀疑与特定的环境污染物暴露有关，但这些污染物在水源中尚未得到确认。在本研究中，我们重点关注中国珠江流域地区，该地区乳腺、卵巢和子宫癌的发病率高。通过结合癌症患者数据、哺乳动物细胞毒性分析以及详尽的历史和当前化学评估，我们首次确定了促进哺乳动物细胞增殖的水源成分，并通过雌激素受体介导的通路证实了它们与这些女性癌症的相关性。因此，之前已经发现能够通过内分泌干扰增强雌激素受体细胞增殖的成分可能是关键因素。基于此，与这种毒理特性（即雌激素样效应）相匹配的成分在水源中进一步被确定，包括（1）有机成分：邻苯二甲酸酯、双酚A、壬基酚和全氟化合物；（2）无机成分：锑、钴、砷和硝酸盐。此外，这些确定的水源成分在水源中的含量与其他高发女性癌症地区相当，这表明这些成分的潜在风险可能不仅限于研究区域。多个证据水平共同表明，长期共同暴露于水源中的雌激素成分可能对乳腺、卵巢和子宫癌的发展至关重要。版权所有 © 2023 Elsevier B.V. 发布。

Breast cancer, ovarian cancer, and uterus cancer are among the most common female cancers. They are suspected to associate with exposures to specific environmental pollutants, which remain unidentified in source waters. In this work, we focused on the Pearl River Basin region in China, which experienced a high incidence of breast, ovarian, and uterus cancers. Combining cancer patient data, mammalian cell cytotoxicity analyses, and exhaustive historical and current chemical assessments, we for the first time identified source water components that promoted proliferation of mammalian cells, and confirmed their association with these female cancers via the estrogen receptor mediated pathway. Therefore, the components that have previously been found to enhance the proliferation of estrogen receptor-containing cells through endocrine disruption could be the crucial factor. Based on this, components that matched with this toxicological characteristic (i.e., estrogen-like effect) were further identified in source waters, including (1) organic components: phthalates, bisphenol A, nonylphenols, and per-/polyfluoroalkyls; (2) inorganic components: Sb, Co, As, and nitrate. Moreover, these identified water components were present at levels comparable to other regions with high female cancer prevalence, suggesting that the potential risk of these components may not be exclusive to the study region. Together, multiple levels of evidence suggested that long-term co-exposures to source water estrogenic components may be important to the development of breast, ovarian, and uterus cancers.Copyright © 2023. Published by Elsevier B.V.