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OPs 和 PYR 的细胞毒性潜力的研究进展:巴基斯坦暴露工人中 PON1 遗传变异的体外细胞毒性和遗传毒性影响。

Insights of OPs and PYR cytotoxic potential Invitro and genotoxic impact on PON1 genetic variant among exposed workers in Pakistan.

机构信息

The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi, 75270, Pakistan.

出版信息

Sci Rep. 2022 Jun 9;12(1):9498. doi: 10.1038/s41598-022-13454-0.

Abstract

Different pesticide chemicals are used to enhance crop yield by protecting from pests. Organophosphate (OPs) and Pyrethroid (PYR) are used in fields of Sanghar, Sindh Pakistan. PON1 an antioxidant enzyme implicated in OPs detoxification may predispose by OPs chronic exposure. This study was conducted to evaluate the toxic potential of active pesticide chemicals at cellular and genetic levels. To examine toxic potential, locally consumed pesticide n = 2 and reference pesticide compounds organophosphate (OPs): Chloropyrifos, Malathion and Pyrethroid (PYR): Cyprmethrin, Cyhalothrin n = 4 were tested against NIH 3T3 cells using MTS assay. Local consumer pesticides demonstrated relevance for half-maximum inhibitory concentration (IC50) 0.00035 mg/mL with selected compound. Malathion IC50 exhibited the highest cytotoxicity among four compounds at 0.0005 mg/mL. On genotoxicity analysis in exposed subjects n = 100 genotypes and alleles n = 200 exhibited significant differences in genotypic and allelic frequencies of pesticide exposed subjects and controls n = 150 (X = 22.9, p = 0.001). Screening of genotypes were performed by PCR- RFLP. Statistical assessment carried out using online software and tools. Results suggested that higher heterozygous genotype A/G (74%) may confer low PON1 metabolic activity towards pesticides in exposed subjects. Findings could be helpful to establish health plans by avoiding toxic chemicals that harming exposed population.

摘要

不同的农药化学品被用于通过保护作物免受虫害来提高作物产量。在巴基斯坦信德省桑加尔地区,使用有机磷(OPs)和拟除虫菊酯(PYR)。PON1 是一种抗氧化酶,参与 OPs 的解毒作用,可能因 OPs 的慢性暴露而预先存在。本研究旨在评估活性农药化学品在细胞和遗传水平上的毒性潜力。为了检查毒性潜力,对当地消费的农药 n = 2 和参考农药化合物有机磷(OPs):氯吡硫磷、马拉硫磷和拟除虫菊酯(PYR):氯氰菊酯、氯氟氰菊酯 n = 4 进行了测试使用 MTS 测定法对 NIH 3T3 细胞进行了测试。当地消费的农药在半最大抑制浓度 (IC50) 方面表现出相关性,其浓度为 0.00035 mg/mL,具有选定的化合物。在四种化合物中,马拉硫磷的 IC50 表现出最高的细胞毒性,为 0.0005 mg/mL。在暴露组 n = 100 个体的遗传毒性分析中,基因型和等位基因 n = 200 个体的基因型和等位基因频率表现出显著差异,暴露组和对照组 n = 150 个体的基因型和等位基因频率表现出显著差异(X = 22.9,p = 0.001)。通过 PCR-RFLP 对基因型进行了筛选。使用在线软件和工具进行了统计评估。结果表明,在暴露组中,更高的杂合基因型 A/G(74%)可能会导致 PON1 对农药的代谢活性降低。这些发现可能有助于通过避免损害暴露人群的有毒化学物质来制定健康计划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1835/9184543/e1f557f8c68c/41598_2022_13454_Fig1_HTML.jpg

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