Molecular Genetics and Cancer Biology Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India.
Erode Cancer Center Hospital, Perundurai Road, Thindal, Erode, Tamil Nadu, 638012, India.
Sci Rep. 2023 Jun 15;13(1):9712. doi: 10.1038/s41598-023-35552-3.
Breast cancer is the third most common cancer in women after skin and lung cancer. Pesticides are of interest in etiologic studies of breast cancer because many pesticides mimic estrogen, a known breast cancer risk factor. In this study, we discerned the toxic role of the pesticides atrazine, dichlorvos, and endosulfan in inducing breast cancer. Various experimental studies, such as biochemical profiling of pesticide-exposed blood samples, comet assays, karyotyping analysis, pesticide and DNA interaction analysis by molecular docking, DNA cleavage, and cell viability assays, have been carried out. Biochemical profiling showed an increased level of blood sugar, WBC, hemoglobin, and blood urea in the patient exposed to pesticides for more than 15 years. The comet assay for DNA damage performed on patients exposed to pesticides and pesticide-treated blood samples revealed more DNA damage at the 50 ng concentration of all three pesticides. Karyotyping analysis showed enlargements in the heterochromatin region and 14pstk+, and 15pstk+in the exposed groups. In molecular docking analysis, atrazine had the highest glide score (- 5.936) and glide energy (- 28.690), which reveals relatively high binding capability with the DNA duplex. The DNA cleavage activity results showed that atrazine caused higher DNA cleavage than the other two pesticides. Cell viability was the lowest at 50 ng/ml (72 h). Statistical analysis performed using SPSS software unveiled a positive correlation (< 0.05) between pesticide exposure and breast cancer. Our findings support attempts to minimize pesticide exposure.
乳腺癌是女性中仅次于皮肤癌和肺癌的第三大常见癌症。在乳腺癌的病因学研究中,农药因其具有雌激素类似物的作用而备受关注,而雌激素是已知的乳腺癌危险因素。在这项研究中,我们发现了莠去津、敌敌畏和硫丹这三种农药在诱导乳腺癌方面的毒性作用。我们进行了各种实验研究,如暴露于农药的血液样本的生化特征分析、彗星试验、核型分析、分子对接分析农药与 DNA 的相互作用、DNA 切割和细胞活力测定。生化特征分析显示,暴露于农药超过 15 年的患者的血糖、白细胞、血红蛋白和血尿素水平升高。对暴露于农药和经农药处理的血液样本的患者进行的 DNA 损伤彗星试验显示,三种农药的 50ng 浓度均导致更多的 DNA 损伤。核型分析显示,暴露组的异染色质区域和 14pstk+、15pstk+均增大。在分子对接分析中,莠去津的滑行评分(-5.936)和滑行能量(-28.690)最高,这表明它与 DNA 双链具有相对较高的结合能力。DNA 切割活性结果表明,莠去津引起的 DNA 切割比其他两种农药更高。细胞活力在 50ng/ml(72h)时最低。使用 SPSS 软件进行的统计分析显示,农药暴露与乳腺癌之间存在正相关(<0.05)。我们的研究结果支持尽量减少农药暴露的尝试。