Dept. Legal Medicine and Toxicology, University of Granada School of Medicine, Spain.
Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Spain.
Chem Biol Interact. 2016 Nov 25;259(Pt B):160-167. doi: 10.1016/j.cbi.2016.04.008. Epub 2016 Apr 7.
Pesticide exposure has been associated with different adverse health effects which may be modulated to some extent by paraoxonase-1 (PON1) activity and genetic polymorphisms. This study assessed seasonal variations in PON1 activity (using paraoxon -POase-, phenylacetate -AREase-, diazoxon -DZOase- and dihydrocoumarin -DHCase- as substrates), erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (using butyrylthiocholine -BuChE- and benzoylcholine -BeChE- as substrates. The study population consisted of intensive agriculture workers regularly exposed to pesticides other than organophosphates and non-exposed controls from Almería (Southeastern Spain). The effect of common genetic polymorphisms of PON1 and BCHE on paraoxonase-1 and cholinesterase activities toward different substrates was also assessed. Linear mixed models were used to compare esterase activities in agricultural workers and control subjects over the two study periods (high and low exposure to pesticides). The significant decrease in AChE and increase in BuChE and BeChE activities observed in workers with respect to control subjects was attributed to pesticide exposure. Workers also had higher levels of AREase, DZOase and, to a lesser extent, of POase, but showed decreased DHCase activity. While PON1 Q192R and PON1 -108C/T gene polymorphisms were significantly associated with all PON1 activities, PON1 L55M showed a significant association with AREase, DZOase and DHCase. BCHE-K (Karlow variant) was significantly associated with lower BeChE activity (but not with BuChE) and BCHE-A (atypical variant) showed no significant association with any cholinesterase activity. These findings suggest that increased PON1, BuChE and BeChE activities in exposed workers might result from an adaptive response against pesticide exposure to compensate for adverse effects at the biochemical level. This response appears to be modulated by PON1 and BCHE gene polymorphisms.
接触农药会导致不同的健康不良影响，而这些影响在一定程度上可以通过对氧磷酶 1（PON1）活性和遗传多态性来调节。本研究评估了 PON1 活性的季节性变化（使用对氧磷- POase-、苯乙酸- AREase-、敌草快- DZOase-和二氢香豆素- DHCase-作为底物）、红细胞乙酰胆碱酯酶（AChE）和血浆胆碱酯酶（使用丁酰硫代胆碱- BuChE-和苯甲酰胆碱- BeChE-作为底物）。研究人群由经常接触除有机磷以外的农药的密集型农业工人和来自阿尔梅里亚（西班牙东南部）的非接触对照者组成。还评估了 PON1 和 BCHE 的常见遗传多态性对不同底物的对氧磷酶-1 和胆碱酯酶活性的影响。线性混合模型用于比较两个研究期间（高和低接触农药）农业工人和对照者的酯酶活性。与对照者相比，工人的 AChE 活性显著降低，BuChE 和 BeChE 活性增加，这归因于农药暴露。工人的 AREase、DZOase 水平升高，而 POase 水平略有升高，但 DHCase 活性降低。PON1 Q192R 和 PON1 -108C/T 基因多态性与所有 PON1 活性显著相关，而 PON1 L55M 与 AREase、DZOase 和 DHCase 显著相关。BCHE-K（Karlow 变体）与较低的 BeChE 活性显著相关（但与 BuChE 无关），而 BCHE-A（非典型变体）与任何胆碱酯酶活性均无显著相关性。这些发现表明，暴露于农药的工人中 PON1、BuChE 和 BeChE 活性的增加可能是对农药暴露的一种适应反应，以补偿生化水平的不良影响。这种反应似乎受到 PON1 和 BCHE 基因多态性的调节。
