PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity.
PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity.
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农场工人母亲和儿童的 PON1 状态作为有机磷敏感性的预测因子。
DOI：
10.1097/01.fpc.0000189796.21770.d3
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发表时间：
2006
影响因子：
2.6
通讯作者：
Eskenazi,Brenda
中科院分区：
文献类型：
--
作者：
Furlong,ClementE;Holland,Nina;Richter,RebeccaJ;Bradman,Asa;Ho,Alan;Eskenazi,Brenda
目的是确定PON1状态作为来自加利福尼亚州萨利纳斯山谷拉美裔母亲和新生儿队列中有机磷杀虫剂敏感性的预测因子，萨利纳斯山谷是一个有机磷杀虫剂使用水平很高的地区。采用高通量双底物活性/分析方法对130名拉丁孕妇及其新生儿的PON1状态进行了研究，该方法绘制了重氮唑（DZO）水解率和对氧磷（PO）水解率。以苯乙酸酯为底物测定芳基酯酶活性（AREase），比较母亲和儿童pon1192基因型间PON1水平。苯乙酸水解不受Q192R多态性的影响。在新生儿中，PON1 （area ase）水平变化了26倍（4.3-110.7 U/ml），在母亲中变化了14倍（19.8-281.4 U/ml）。平均而言，儿童的PON1水平比母亲低4倍（P< 0.001）。新生儿的平均PON1水平与表达人类PON1 Q192或PON1 R192的转基因小鼠中报道的hPON1水平相当，从而可以预测对毒死蜱（CPO）和DZO的相对敏感性。在同一拉丁裔队列中，母亲和儿童对DZO的敏感性预测变异性范围为65倍，对CPO的预测变异性范围为131至164倍。总体而言，这些发现表明，该队列中的许多新生儿和一些母亲由于其PON1状态而更容易受到特定有机磷农药暴露的不良影响。特别值得关注的是暴露于低PON1状态的孕妇和新生儿。
The objective was to determine PON1 status as a predictor for organophosphorus insecticide sensitivity in a cohort of Latina mothers and newborns from the Salinas Valley, California, an area with high levels of organophosphorus insecticide use. PON1 status was established for 130 pregnant Latina women and their newborns using a high-throughput two substrate activity/analysis method which plots rates of diazoxon (DZO) hydrolysis against rates of paraoxon (PO) hydrolysis. Arylesterase activity (AREase) was determined using phenylacetate as a substrate, allowing comparison of PON1 levels across PON1 192 genotypes in mothers and children. Phenylacetate hydrolysis is not affected by the Q192R polymorphism. Among newborns, levels of PON1 (AREase) varied by 26-fold (4.3–110.7 U/ml) and among mothers by 14-fold (19.8–281.4 U/ml). On average, children's PON1 levels were four-fold lower than the mothers' PON1 levels (P< 0.001). Average PON1 levels in newborns were comparable with reported hPON1 levels in transgenic mice expressing human PON1 Q192 or PON1 R192, allowing for prediction of relative sensitivity to chlorpyrifos oxon (CPO) and DZO. The predicted range of variability in sensitivity of mothers and children in the same Latino cohort was 65-fold for DZO and 131 to 164-fold for CPO. Overall, these findings indicate that many of the newborns and some of the mothers in this cohort would be more susceptible to the adverse effects of specific organophosphorus pesticide exposure due to their PON1 status. Of particular concern are exposures of pregnant mothers and newborns with low PON1 status.