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Malathion induced cancer-linked gene expression in human lymphocytes.
Environmental Research ( IF 7.7 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.envres.2020.109131
Ramakrishnan Anjitha 1 , Anet Antony 1 , Olakkaran Shilpa 1 , Kizhakke P Anupama 1 , Shanthala Mallikarjunaiah 2 , Hunasanahally P Gurushankara 1
Affiliation  

BACKGROUND Malathion is the most widely used organophosphate pesticide in agriculture. Increasing cancer incidence in agricultural workers and their children links to the exposure of malathion. Identification of genes involved in the process of carcinogenesis is essential for exploring the role of malathion. The alteration in gene expression by malathion in human lymphocytes has not been explored yet, although hematological malignancies are rampant in humans. OBJECTIVE This study investigates the malathion induced expression of cancer associated genes in human lymphocytes. METHODS Human lymphocyte viability and colony-forming ability were analyzed in malathion treated and control groups. Gene expression profile in control and malathion treated human lymphocytes were performed using a microarray platform. The genes which have significant functions and those involved in different pathways were analyzed using the DAVID database. Differential gene expression upon malathion exposure was validated by quantitative real-time (qRT)-PCR. RESULTS Malathion caused a concentration-dependent reduction in human lymphocyte viability. At low concentration (50 μg/mL) of malathion treatment, human lymphocytes were viable indicating that low concentration of malathion is not cytotoxic and induces the colony formation. Total of 659 genes (15%) were up regulated and 3729 genes (85%) were down regulated in malathion treated human lymphocytes. About 57 cancer associated genes related to the growth and differentiation of B and T cells, immunoglobulin production, haematopoiesis, tumor suppression, oncogenes and signal transduction pathways like MAPK and RAS were induced by malathion. CONCLUSION This study evidences the carcinogenic nature of malathion. Low concentration of this pesticide is not cytotoxic and induces differentially regulated genes in human lymphocytes, which are involved in the initiation, progression, and pathogenesis of cancer.

中文翻译:

马拉硫磷诱导人淋巴细胞中癌症相关基因的表达。

背景技术马拉硫磷是农业中使用最广泛的有机磷酸盐农药。农业工人及其子女的癌症发病率增加与马拉硫磷的暴露有关。鉴定参与致癌过程的基因对于探索马拉硫磷的作用至关重要。尽管血液恶性肿瘤在人类中普遍存在,但尚未探索人类淋巴细胞中马拉硫磷引起的基因表达改变。目的本研究调查了马拉硫磷诱导的人类淋巴细胞癌相关基因的表达。方法分析马拉硫磷治疗组和对照组的人淋巴细胞活力和集落形成能力。使用微阵列平台进行对照和马拉松处理的人淋巴细胞中的基因表达谱。使用DAVID数据库分析了具有重要功能的基因和涉及不同途径的基因。通过定量实时(qRT)-PCR验证了马拉硫磷暴露后的差异基因表达。结果马拉硫磷引起了人类淋巴细胞活力的浓度依赖性降低。在低浓度(50μg/ mL)的马拉硫磷治疗下,人淋巴细胞是可行的,这表明低浓度的马拉硫磷没有细胞毒性,并能诱导菌落形成。在马拉松处理的人淋巴细胞中,共有659个基因(占15%)被上调,而3729个基因(占占85%)被下调。大约57个与癌症相关的基因与B细胞和T细胞的生长和分化,免疫球蛋白的产生,造血作用,肿瘤抑制,马拉硫磷诱导癌基因和信号转导途径如MAPK和RAS。结论这项研究证明了马拉硫磷的致癌性。低浓度的这种农药不会产生细胞毒性,并会在人类淋巴细胞中诱导差异调节的基因,这些基因与癌症的发生,发展和发病机理有关。
更新日期:2020-01-11
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