The Impact of Pesticides - Academy Publish

The Role of Human Paraoxonase-1 (Pon1) as a Modulatorof Organophosphorous Pesticide Adverse EffectsDr. Betzabet Quintanilla-Vega, Dr. Norma Pérez-Herrera and Dr. AuroraElizabeth Rojas-GarcíaAbbreviations: AChE, acethylcholinesterase; BER, base excision repair; CYP,cytochrome P450; CBT, childhood brain tumors; DAP, dialkylphosphates; DMP,dimethylphosphate; LBW, low birth weight; MN, micronucleus; OP,organophosphate; PON1, human paraoxonase 1; SB, spina bifida; SNP, singlenucleotide polymorphism.ABSTRACTGene-environment interactions have attracted attention in last decades, since theyinfluence xenobiotic toxicokinetics, such as organophosphate (OP) pesticides,modifying their toxicity. Regarding OP, one of the genes is human serumparaoxonase-1 (PON1), an esterase predominantly synthesized in the liver andassociated with high-density lipoproteins (HDL). PON1 is involved in deactivationof some OP and nerve agents. Plasma PON1 activity varies among individuals by acombination of genetic interactions with environmental-dietary factors, leading to a40-fold variation. More than 200 SNPs have been identified in PON1 gene, butgenetic variations focus on a few in the promoter and coding regions affecting eitherthe amount of the enzyme or the affinity for specific substrates. This chapter willdiscuss the contribution of PON1 polymorphisms, particularly those in the codingregion, Q192R and L55M, which have shown more consistently to enhance theassociations between OP exposure and adverse effects. OP exposure is of publichealth concern in developing countries, not only to workers (agriculture andmanufacture) but to their families. Individuals carrying the risk alleles are moresusceptible toward alterations on semen quality, neurological function, DNAintegrity, among others, as well as brain tumors, neurodevelopment and cognitivealterations and malformations in children by paternal or prenatal OP exposures.Studies have shown that PON1 polymorphisms are relevant risk factors for havingpeople affected by OP exposure but not consistently, therefore, the exact role ofPON1 genetic variation on the susceptibility to OP toxicity is an important questionthat remains to be elucidated.INTRODUCTIONEpidemiological studies have shown the global impact of anticholinesterasepesticides, after acute and chronic poisoning on public health worldwide, includingdeveloped and developing countries. The magnitude of acute poisoning is difficultto know, but it has been estimated on 250,000-500,000 events with 30,000 to300,000 fatalities yearly and organophosphate (OP) pesticides are often the mostinvolved. Registers show that OP and carbamates are involved in 40% of accidentalpesticide poisonings in the developing world. A high proportion of poisonings inAcademyPublish.org - The Impact of Pesticides63