title: Human paraoxonase 1 hydrolysis of nanomolar chlorpyrifos-oxon concentrations is unaffected by phenotype or Q192R genotype.
abstract: The organophosphorus insecticide chlorpyrifos has been widely used. Its active metabolite chlorpyrifos-oxon (CPO) is a potent anticholinesterase and is detoxified by paraoxonase 1 (PON1). PON1 activity is influenced by numerous factors including a Q192R polymorphism. Using forty human blood samples bearing homozygous genotypes and either high or low activity phenotypes (as determined by high concentration assays of paraoxon and diazoxon hydrolysis) the serum PON1 hydrolysis of high (320 μM) and low (178 nM) CPO concentrations was assessed using direct or indirect spectrophotometric methods, respectively. PON1 activity at high CPO concentration reflected the phenotype and genotype differences; subjects with the high activity phenotype and homozygous for the PON1R192 alloform hydrolyzed significantly more CPO than subjects with the low activity phenotype and/or PON1Q192 alloform (high RR=11023±722, low RR=9467±798, high QQ=8809±672, low QQ=6030±1015 μmol CPO hydrolyzed/min/L serum). However, PON1 hydrolysis of CPO at the lower, more environmentally relevant concentration showed no significant differences between the PON1192 genotypes and/or between high and low activity phenotypes (high RR=231±27, low RR=219±52, high QQ=193±59, low QQ=185±43 nmol CPO/min/L serum). Low CPO concentrations were probably not saturating, so PON1 did not display maximal velocity and the PON1 genotype/phenotype might not influence the extent of metabolism at environmental exposures.
authors.affiliation: Basic Sciences Department and Center for Environmental Health Sciences, College of Veterinary Medicine, P.O. Box 6100, 240 Wise Center Drive, Mississippi State University, Mississippi State, MS, USA 39762-6100. Electronic address: hcoombes@umaryland.edu.
authors.forename: R Hunter
authors.initials: RH
authors.lastname: Coombes
authors.affiliation: Basic Sciences Department and Center for Environmental Health Sciences, College of Veterinary Medicine, P.O. Box 6100, 240 Wise Center Drive, Mississippi State University, Mississippi State, MS, USA 39762-6100. Electronic address: emeek@cvm.msstate.edu.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Meek
authors.affiliation: Basic Sciences Department and Center for Environmental Health Sciences, College of Veterinary Medicine, P.O. Box 6100, 240 Wise Center Drive, Mississippi State University, Mississippi State, MS, USA 39762-6100. Electronic address: dail@cvm.msstate.edu.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Dail
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology: Entomology Unit and Center for Environmental Health Sciences, Mississippi State University, Mississippi State, MS, USA 39762. Electronic address: hwc2@msstate.edu.
authors.forename: Howard W
authors.initials: HW
authors.lastname: Chambers
authors.affiliation: Basic Sciences Department and Center for Environmental Health Sciences, College of Veterinary Medicine, P.O. Box 6100, 240 Wise Center Drive, Mississippi State University, Mississippi State, MS, USA 39762-6100. Electronic address: chambers@cvm.msstate.edu.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Chambers
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D004390:Chlorpyrifos / Q000031:analogs & derivatives* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D006868:Hydrolysis; D007306:Insecticides / Q000378:metabolism*; D007700:Kinetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D013053:Spectrophotometry
chemical_list: D007306:Insecticides; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D004390:Chlorpyrifos
keywords: Chlorpyrifos-oxon; PON1; Paraoxonase 1; Polymorphism
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