Article

PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity

University of California, Berkeley, Berkeley, California, United States
Pharmacogenetics and Genomics (Impact Factor: 3.48). 04/2006; 16(3):183-90. DOI: 10.1097/01.fpc.0000189796.21770.d3
Source: PubMed

ABSTRACT

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 PON1192 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 PON1Q192 or PON1R192, 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.

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    • "Considerable residues of chlorpyrifos have been found in food chain [36]. Chlorpyrifos also adversely affects the nontarget systems including nervous system disorders, birth defects, low birth weights, immune system abnormalities, and endocrine disruption [37] [38]. Moreover , bladder cancer and chromosome damage are also found to be associated with exposure to chlorpyrifos [39]. "
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    • "Since the polymorphism Q192R confers differential catalytic activity against these two substrates , the plot splits the population into the three functional position 192 genotype (QQ, QR, and RR). A third assay that measures rates of PA hydrolysis at low salt concentration reveals plasma PON1 activity since under these assay conditions, the PON1 Q192R polymorphism does not influence PON1 catalytic activity against PA [9] (Furlong et al.). For this assay, rates of hydrolysis of PA were measured at 270 nm for 4 min at 25 • C using 20 ␮L of plasma diluted 1:80 in dilution buffer. "

    Full-text · Dataset · Aug 2015
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    • "Since the polymorphism Q192R confers differential catalytic activity against these two substrates , the plot splits the population into the three functional position 192 genotype (QQ, QR, and RR). A third assay that measures rates of PA hydrolysis at low salt concentration reveals plasma PON1 activity since under these assay conditions, the PON1 Q192R polymorphism does not influence PON1 catalytic activity against PA [9] (Furlong et al.). For this assay, rates of hydrolysis of PA were measured at 270 nm for 4 min at 25 • C using 20 ␮L of plasma diluted 1:80 in dilution buffer. "
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