Centro de Investigación y Estudios Avanzados Maule (CIEAM), Universidad Católica del Maule, Talca, Chile.
Centro de Investigación en Neuropsicología y Neurociencias Cognitivas (CINPSI-Neurocog), Universidad Católica del Maule, Talca, Chile.
Environ Mol Mutagen. 2022 Apr;63(4):215-226. doi: 10.1002/em.22485. Epub 2022 May 26.
The active ingredients in pesticides are known to be genotoxic that can cause mutations, chromosomal aberrations, or other types of DNA damage. Early detection of genotoxicity reduces the risk of developing diseases such as cancer or suffering from reproductive disorders. In turn, the genotoxic risk depends on the intrinsic capability of the individual to metabolize and eliminate the xenobiotic from the organism. This study aimed to determine if two polymorphisms of paraoxonase-1 (PON1), which is involved in the metabolism of several organophosphate (OP) pesticides, are predictors of susceptibility to DNA damage in agricultural workers and inhabitants of rural areas chronically exposed to pesticides. A cross-sectional study was made considering three groups: agricultural workers (occupational exposure, OE, n = 85), rural inhabitants (environmental exposure, EE, n = 60), and an unexposed group conformed by people living far from agricultural areas (U, n = 33). The level of individual DNA damage was measured using the comet assay, and genotyping was done to determine the PON1 Q192R and L55M polymorphisms. Acetylcholinesterase and butyrilcholinesterase activities were also measured to determine exposure to OP. Individuals belonging to EE and OE groups displayed higher levels of DNA damage compared with U group (p < .001). OP exposure was the main predictor of genotoxicity (β = 16.19; 95% CI: 1.85, 30.52), instead of PON1 polymorphisms (β = -12.20; 95% CI: -27.87, 3.48). These results confirm the genotoxic effects of pesticide exposure and suggest that the catalytic efficiency of PON1 to metabolize OP pesticides becomes negligible in individuals with a history of long-term environmental or occupational exposure to these substances.
农药中的活性成分已知具有遗传毒性,可导致突变、染色体畸变或其他类型的 DNA 损伤。遗传毒性的早期检测可降低患癌症或生殖障碍等疾病的风险。反过来,遗传毒性风险取决于个体代谢和消除机体中外源物质的内在能力。本研究旨在确定参与几种有机磷 (OP) 农药代谢的对氧磷酶 1 (PON1) 的两个多态性是否可预测长期接触农药的农业工人和农村居民对 DNA 损伤的易感性。考虑到三个组进行了一项横断面研究:农业工人(职业暴露,OE,n = 85)、农村居民(环境暴露,EE,n = 60)和由远离农业区的人组成的未暴露组(U,n = 33)。使用彗星试验测量个体 DNA 损伤水平,并进行基因分型以确定 PON1 Q192R 和 L55M 多态性。还测量了乙酰胆碱酯酶和丁酰胆碱酯酶活性以确定 OP 的暴露情况。与 U 组相比,EE 和 OE 组的个体 DNA 损伤水平更高(p <.001)。OP 暴露是遗传毒性的主要预测因素(β = 16.19;95%CI:1.85,30.52),而不是 PON1 多态性(β = -12.20;95%CI:-27.87,3.48)。这些结果证实了农药暴露的遗传毒性作用,并表明在长期暴露于这些物质的环境或职业的个体中,PON1 代谢 OP 农药的催化效率变得微不足道。