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Extramural Research

2006 Progress Report: PON1 as a Predictor of Differential Susceptibility of Children to Organophosphate Pesticides

EPA Grant Number: R832734
Title: PON1 as a Predictor of Differential Susceptibility of Children to Organophosphate Pesticides
Investigators: Eskenazi, Brenda , Barr, Dana , Bradman, Asa , Holland, Nina T. , Hubbard, Alan
Current Investigators: Eskenazi, Brenda , Barr, Dana , Bradman, Asa , Harley, Kim , Holland, Nina T. , Hubbard, Alan
Institution: University of California - Berkeley
EPA Project Officer: Callan, Richard
Project Period: March 20, 2006 through February 28, 2009 (Extended to February 28, 2011)
Project Period Covered by this Report: March 20, 2006 through February 28, 2007
Project Amount: $749,987
RFA: Early Indicators of Environmentally Induced Disease (2004)
Research Category: Health Effects , Human Health

Description:

Objective:

Organophosphate (OP) pesticide exposure is widespread in the U.S. population. Based primarily on animal studies, there is significant evidence that low-level exposure to OP pesticides can have adverse health effects in children (Eskenazi, et al., 2004; Young, et al., 2005). However, not all individuals may be equally susceptible. A gene, PON1, has been identified that may contribute to differential sensitivity to OP exposure. Our goal is to determine whether PON1 genotype and phenotype modify the association of OP pesticide exposure and neurodevelopmental outcomes in children.

Progress Summary:

This year, we finished blood collection, processing, and banking of samples from all 5-year-old children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (Eskenazi, et al., 2003). Collection in 7-year-old children and their mothers has begun this year. We conducted extensive validation experiments for PON1 enzyme activities on stored and freshly collected blood, established a range of variability for OPs in blood, and also performed DNA isolation for high-throughput genotyping from over 400 children and >500 mothers from the CHAMACOS cohort. Neurodevelopmental assessments were completed for 328 5-year-old children, for whom longitudinal data are also available (including the Brazelton and Bayley tests), and have also begun in 7-year-old children.

Future Activities:

We plan to complete enzyme activity assays in cord and child blood (5 years old) this year. These data will be used to determine whether PON1 genotype and PON1 activity are associated with child neurodevelopment (Specific Aim 2). Further validation experiments will be run at CDC to determine optimal volume and protocol for OP analysis in cord blood.


Journal Articles on this Report : 5 Displayed | Download in RIS Format

Other project views: All 90 publications 21 publications in selected types All 21 journal articles

Type Citation Project Document Sources
Journal Article Eskenazi B. Centros de investigación de salud medioambiental y prevención de enfermedades de niños. Desde 1998 al presente. Acta Toxicologica Argentina 2006;14(Suppl):60-62. R832734 (2006)
R831710 (2005)
R831710 (Final)
R831710C001 (2007)
  • Full-text: ATA - PDF
    Exit
  • Journal Article Eskenazi B, Bradman A, Harley K, Holland N. Indicadores biologicos de exposicion a pesticidas y su relacion con la salud de los ninos. Acta Toxicologica Argentina 2006;14(Supplement):63-65. R832734 (2006)
    R831710 (2005)
    R831710C001 (2007)
    R831710C002 (2007)
    not available
    Journal Article Holland N, Furlong C, Bastaki M, Richter R, Bradman A, Huen K, Beckman K, Eskenazi B. Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns. Environmental Health Perspectives 2006;114(7):985-991. R832734 (2006)
    R832734 (2007)
    R832734 (Final)
    R831709 (2005)
    R831709 (2006)
    R831709 (2007)
    R831709C002 (2006)
    R831710 (2004)
    R831710 (2005)
    R831710 (Final)
    R831710C001 (2007)
    R831710C003 (2006)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Neri M, Bonassi S, Knudsen LE, Sram RJ, Holland N, Ugolini D, Merlo DF. Children’s exposure to environmental pollutants and biomarkers of genetic damage: I. Overview and critical issues. Mutation Research-Reviews in Mutation Research 2006;612(1):1-13. R832734 (2006)
    R832734 (2007)
    R832734 (Final)
    R831710 (Final)
    R831710C003 (2006)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Journal Article Neri M, Ugolini D, Bonassi S, Fucic A, Holland N, Knudsen LE, Sram RJ, Ceppi M, Bocchini V, Merlo DF. Children’s exposure to environmental pollutants and biomarkers of genetic damage: II. Results of a comprehensive literature search and meta-analysis. Mutation Research-Reviews in Mutation Research 2006;612(1):14-39. R832734 (2006)
    R832734 (Final)
    R831710 (Final)
    R831710C003 (2006)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
    Exit
  • Other: ScienceDirect-PDF
    Exit
  • Supplemental Keywords:

    PON1, organophosphates, pesticides, neurodevelopment,, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, Genetics, Health Risk Assessment, Biochemistry, Children's Health, Environmental Policy, Risk Assessment, pesticide exposure, farmworkers, developmental neurotoxicity, gene-environment interaction, Human Health Risk Assessment, human enzyme paraoxonase, susceptibility, genetic polymorphisms, children's vulnerablity, assessment of exposure, developmental disorders

    Relevant Websites:

    http://ehs.sph.berkeley.edu/chamacos/ Exit
    http://ehs.sph.berkeley.edu/Holland/Genomics/genomics.html Exit

    Progress and Final Reports:
    Original Abstract
    2007 Progress Report
    2009 Progress Report
    Final Report

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    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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