The Impact of Pesticides - Academy Publish

three percent of case parents reside in rural areas where pesticides (including OP)use is frequent in agriculture activities. Children with -108CT, 192RR and55LM/MM genotypes of PON1 and the haplotypes 221 and 222 (for PON1 C-108T,L55M and Q192R, respectively) were significantly associated with the risk forhaving a child with SB. PON1 -108CT, 55LM and 192RR genotypes were relevantin mothers, mothers/fathers and fathers, respectively. Albeit the associations ofPON1 genotype or phenotype with altered child development, additional research isneeded to further confirm the relationship with OP paternal exposures, highlightingthe risk of OP susceptibility not only to parents but also to their offspring.CONCLUDING REMARKSGene-environment interactions regarding pesticide toxicity is a multifactorial eventinvolving genetic variability and complex pesticide exposure scenarios that makethe positive or negative interactions between OP exposure and PON1 geneticpolymorphisms with adverse toxic effects difficult to interpret. Results about therole of different PON1 genetic polymorphisms on modulating OP toxicity are notconsistent, mainly due to factors such as relative small sample size, not accurate OPexposure characterization, particularly chronic exposures, complex pesticideexposures to many active ingredients, the inclusion of only one-two PON1polymorphisms, and the lack of including other OP metabolizing enzymepolymorphisms. Additionally, one of the most studied polymorphisms, PON1Q192R, is substrate-dependent; thus the amino acid substitution (Arg/Gln)determines the rates of hydrolysis of different substrates, thereby the R and Q allelesmay have a positive influence in the toxicity of some OP and a negative influence inthe toxicity of others, this is, the effect of this PON1 polymorphism is likely to beexposure specific. Some of these limitations have not been resolved. Finally, sinceother environmental factors such as diet modify the enzymatic activity, PON1phenotype has to be considered while evaluating OP risk assessment. Therefore, noconclusions can be given yet and further studies are necessary to establish PON1role in OP toxicity.REFERENCESAndroutsopoulos VP, Kanavouras K, Tsatsakis AM. 2011. Role of paraoxonase 1(PON1) in organophosphate metabolism: Implications in neurodegenerativediseases. Toxicol Appl Pharmacol 256:418-424.Baldi I, Filleul L, Mohammed-Brahim B, Letenneur L, Dartiguess J-F, Brochard P.2001. Neurodegenerative diseases and exposure to pesticides in the elderly. Am JEpidemiol 157: 409-414.Benmoyal-Segal L, Vander T, Shifman S, Bryk B, Ebstein R, Marcus EL, StessmanJ, Darvasi A, Herishanu Y, Friedman A, Soreq H. 2005.Acetylcholinesterase/paraoxonase interactions increase the risk of insecticideinduced Parkinson’s disease. FASEB J 19:452–454.Berkowitz GS, Wetmur JG, Birman-Deych E, Obel J, Lapinski RH, Godbold JH,Holzman IR, Wolff MS. 2004. In utero pesticide exposure, maternal paraoxonaseactivity, and head circumference. Environ Health Perspect 112:388-391.AcademyPublish.org - The Impact of Pesticides71