■砷的致癌作用是与乳腺癌有关的争议主题。在我们目前的研究中,我们旨在通过用1μM三氧化二砷(As2O3)中毒MCF-10A和MCF-7细胞3周(3w)和6周(6w)来模拟慢性低水平砷暴露对乳腺细胞的影响,分别。
■我们通过各种试验评估了细胞对As2O3的反应,包括共聚焦荧光显微镜,用于细胞周期分析的流式细胞术,Transwell侵袭试验,划痕试验,和菌落测定。此外,我们使用下一代测序技术分析了所有暴露细胞的突变负荷。
■我们的研究结果表明,As2O3对正常细胞有轻微的致癌作用,暴露6周后没有明确的恶性转化证据。在乳腺癌细胞的情况下,As2O3表现出双重效应,抑制和刺激。它导致6周时集落形成能力降低,同时增强细胞的侵袭能力。由As2O3暴露引发的突变分布在具有肿瘤抑制和致癌功能的基因中。两种细胞系共有五种突变,涉及以下基因:激酶插入结构域受体(KDR)(c.798+54G>A),集落刺激因子1受体(CSF1R)(c.*37AC>C,c.*35C>TC),染色质亚家族B成员1(SMARCB1)的SWI/SNF相关基质相关肌动蛋白依赖性调节因子(c.1119-41C>T),和Fms样酪氨酸激酶3(FLT3)(c.1310-3T>C)。此外,人表皮生长因子受体4(ERBB4/HER4)(c.421+58A>G)和人表皮生长因子受体2(HER2/ERBB2)(c.2307+46A>G)突变仅在暴露于As2O3的MCF-10A细胞中发现。此外,MCF-7细胞在KIT原癌基因(KIT)(c.1594G>A)和TP53(c.215C>G)中表现出独特的突变。
■总之,我们的研究表明,6周暴露于砷对正常乳腺细胞具有有限的致癌作用,对乳腺癌细胞具有双重作用。
UNASSIGNED: The
carcinogenic effect of arsenic is a subject of controversy in relation to breast cancer. In our current research, we aimed to simulate the effects of chronic low-level arsenic exposure on breast cells by intoxicating MCF-10A and MCF-7 cells with 1 μM Arsenic trioxide (As2O3) for 3 weeks (3w) and 6 weeks (6w), respectively.
UNASSIGNED: We assessed the cellular responses to As2O3 through various assays, including confocal fluorescence microscopy, flow cytometry for cell cycle analysis, Transwell invasion assay, scratch assay, and colony assay. Additionally, we analyzed the mutation burden in all the exposed cells by using the next generation sequencing technology.
UNASSIGNED: Our findings indicate that As2O3 has a minor
carcinogenic effect in normal cells, with no definitive evidence of malignant transformation observed after 6 weeks of exposure. In the case of breast cancer cells, As2O3 exhibits a dual effect, both inhibitory and stimulatory. It leads to reduced colony formation ability at 6 weeks, while enhancing the cells\' ability for invasion. The mutations triggered by As2O3 exposure are distributed across genes with both tumor-suppressive and oncogenic functions. Five mutations are common to both cell lines, involving the following genes: Kinase Insert Domain Receptor (KDR) (c.798+54G>A), Colony Stimulating Factor 1 Receptor (CSF1R) (c.*37AC>C, c.*35C>TC), SWI/SNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily B Member 1 (SMARCB1) (c.1119-41C>T), and Fms-like Tyrosine Kinase 3 (FLT3) (c.1310-3T>C). Additionally, Human Epidermal Growth Factor Receptor 4 (ERBB4/HER4) (c.421+58A>G) and Human Epidermal Growth Factor Receptor 2 (HER2/ERBB2) (c.2307+46A>G) mutations were exclusively found in MCF-10A cells exposed to As2O3. Furthermore, MCF-7 cells exhibited unique mutations in the KIT Proto-Oncogene (KIT) (c.1594G>A) and TP53 (c.215C>G).
UNASSIGNED: In summary, our study reveals that a 6-weeks exposure to arsenic has a limited
carcinogenic effect in normal breast cells and a dual role in breast cancer cells.