Department of Zoology, School of Biological Sciences, Central University of Kerala, Periya, 671 320, Kasaragod, Kerala, India.
Center for Applied Genetics, Department of Studies in Zoology, Bangalore University, Jnanabharathi, Bengaluru, 560 056, Karnataka, India.
Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
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.
This study investigates the malathion induced expression of cancer associated genes in human lymphocytes.
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.
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.
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.
马拉硫磷是农业中使用最广泛的有机磷农药。农业工人及其子女癌症发病率的增加与马拉硫磷的接触有关。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。尽管血液系统恶性肿瘤在人类中很普遍，但马拉硫磷对人淋巴细胞中基因表达的改变尚未得到探索。
本研究调查了马拉硫磷对人淋巴细胞中癌相关基因表达的诱导作用。
在马拉硫磷处理组和对照组中分析人淋巴细胞的活力和集落形成能力。使用微阵列平台对对照组和马拉硫磷处理组的人淋巴细胞进行基因表达谱分析。使用 DAVID 数据库分析具有显著功能和涉及不同途径的基因。通过定量实时（qRT）-PCR 验证马拉硫磷暴露后的差异基因表达。
马拉硫磷导致人淋巴细胞活力呈浓度依赖性下降。在低浓度（50μg/mL）马拉硫磷处理时，人淋巴细胞仍具有活力，表明低浓度的马拉硫磷无细胞毒性，并诱导集落形成。马拉硫磷处理的人淋巴细胞中总共有 659 个基因（15%）上调，3729 个基因（85%）下调。马拉硫磷诱导了与 B 和 T 细胞生长和分化、免疫球蛋白产生、造血、肿瘤抑制、癌基因以及 MAPK 和 RAS 等信号转导途径相关的 57 个与癌症相关的基因。
本研究证明了马拉硫磷的致癌性质。这种农药的低浓度无细胞毒性，并诱导人淋巴细胞中差异调节的基因，这些基因参与癌症的起始、进展和发病机制。
