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The study of pesticides induced genotoxicity in occupational workers.

Cytogenetic damage in individuals, occupational^ exposed to pesticides has received the attention of investigators in several countries, but no definitive conclusion has yet been drawn. Animal studies also indicated that pesticides may be metabolized by cytochrome P 450 (CYP1A1, CYP3A5) enzymes, paraoxonase (PON1), or glutathione-S-transferases (GSTM1, GSTT1 and GSTP1). However, little is known about the genotoxicity of pesticides in people with various genetic polymorphisms of human xenobiotic metabolizing enzymes coding genes.

The present study conducted on 230 samples (115 each from pesticide exposed and control subjects), was aimed to evaluate the pesticides induced genotoxicity and to correlate genotoxicity with genetic polymorphism of CYP1A1, CYP3A5, PON1, GSTM1, GSTT1, GSTP1 and NAT2 enzymes coding genes. Demographic data (age, gender, etc.) plus data on medical (exposure to X-ray, medication, era), lifestyle (smoking, alcohol, diet, etc), illness (any kind of acute and chronic illness), symptoms (symptoms for the chronic exposure, use of protective measures, type of exposure, type of pesticide used, etc.) were collected through questionnaire. The data revealed that none of them had been using any kind of protective measures which is the main cause of toxicity.

All the occupational workers were exclusively handling organophosphate pesticides (OPs) that were pirimiphos methyl, chlorpyrifos, temephos and malathion. Pesticide analysis in blood sample was done using gas chromatography. The DNA damage was quantified in lymphocytes on single cell gel electrophoresis and apoptosis was studied using DNA fragmentation analysis.

Study could record several fold organophosphate levels in the blood of pesticide exposed subjects compared to controls. Although some amount of OPs was also found in healthy controls but it was not significant. The individuals having pesticide exposure had a significantly greater DNA damage measured using DNA tail moment. Six of the exposed subjects showed DNA fragmentation (apoptosis) associated with duration of exposure to pesticide and age. The prevalence of the genetic polymorphism of CyP1A1, CYP3A5, PON1, GSTM1, GSTT1, GSTP1 and NAT2 xenobiotic polymorphism was significantly same in pesticide exposed and control subjects. The pesticide exposed individuals with GSTM1 null genotypes, metabolic GSTP1 lle/Val and PON1 Q192R and L55M genes were found to modulate DNA damage.

Genetic polymorphism of PON1 at Q192R and L55M modulated paraoxonase activity against paraoxon and not against phenyl acetate. The paraoxonase activity was in the order of; PON 1192 RR > - QR > - QQ and PON 155 LL > - LM > - MM. The pesticide exposed individuals with QQ and MM had greater DNA damage compared to different isoforms of PON1 Q192R and L55M. The QQ and MM exposed individuals had lower paraoxonase activity that was unable to hydrolyze OPs leading to accumulation of products and thereby inducing DNA damage, while PON1 R/R and L/L individuals had a higher paraoxonase activity, hydrolyze OPs rapidly and therefore had reduced DNA damage. Hence the low metabolizers are more susceptible towards genotoxicity. The determination of QR and LM genotype and phenotype may be helpful in providing baseline data of PON1 status and as an individual marker of susceptibility in further population studies addressing health and diseases in pesticide-exposed population. Slow acetylation was more prevalent in pesticide exposed subjects with smoking compared to non smokers which suggests an association in smoking, pesticide and slow acetylation. The study is therefore helpful in identifying the individual markers of susceptibility and toxicity toward pesticides. The present data can help to explore the relationship of xenobiotic metabolizing enzymes with disease risk and drug effects in Indian population.

Publication

Singh, S., Kumar, V., Thakur, S., Banerjee, B.D., Grover, S.S., Rawat, D.S., Pasha, ST., Jain, S.K., Lai, S. and Rai, A. Genetic polymorphism of glutathione-S-transferase M1 and T1 in Delhi population of northern India. Environ Toxicol Pharmacol 28: 25, 2009.

Satyender Singh

Dr. S.K. Jain

Centre for Epidemiology and Parasitic Diseases

National Centre for Disease Control

Delhi
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Title Annotation:ABSTRACTS: Some Research Projects Completed Recently
Author:Singh, Satyender; Jain, S.K.
Publication:ICMR Bulletin
Article Type:Report
Date:May 1, 2011
Words:627
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