Center for Epidemiology and Parasitic Diseases

Delhi, India

Center for Epidemiology and Parasitic Diseases

Delhi, India
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Singh S.,National Center for Disease Control 22 | Kumar V.,University of Delhi | Vashisht K.,National Center for Disease Control 22 | Singh P.,National Center for Disease Control 22 | And 7 more authors.
Toxicology and Applied Pharmacology | Year: 2011

Organophosphate pesticides (OPs) are primarily metabolized by several xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticide-exposed workers. The present study was designed to determine the role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to OPs. We examined 284 subjects including 150 workers occupationally exposed to OPs and 134 normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using PCR-RFLP. The results revealed that the PONase activity toward paraoxonase and AChE activity was found significantly lowered in workers as compared to control subjects (p<. 0.001). Workers showed significantly higher DNA damage compared to control subjects (14.37 ± 2.15 vs. 6.24 ± 1.37 tail% DNA, p<. 0.001). Further, the workers with CYP2D6 3PM and PON1 (QQ and MM) genotypes were found to have significantly higher DNA damage when compared to other genotypes (p<. 0.05). In addition, significant increase in DNA damage was also observed in workers with concomitant presence of certain CYP2D6 and PON1 (Q192R and L55M) genotypes which need further extensive studies. In conclusion, the results indicate that the PON1 and CYP2D6 genotypes can modulate DNA damage elicited by some OPs possibly through gene-environment interactions. © 2011 Elsevier Inc.


Singh S.,National Center for Disease Control | Kumar V.,University of Delhi | Thakur S.,National Center for Disease Control | Thakur S.,University of Texas Health Science Center at San Antonio | And 9 more authors.
Toxicology and Applied Pharmacology | Year: 2011

Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The results revealed that PON1 activity toward paraoxon (179.19±39.36 vs. 241.52±42.32nmol/min/ml in controls) and phenylacetate (112.74±17.37 vs. 134.28±25.49μmol/min/ml in controls) was significantly lower in workers than in control subjects (p<0.001). No significant difference was observed in the distribution of genotypes and allelic frequencies of PON1192QR (Gln/Arg) and PON155LM (Leu/Met) in workers and control subjects (p>0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p<0.001). For PON155LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p<0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p<0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs (p<0.05). The results indicate that the individuals with PON1 Q/Q and M/M genotypes are more susceptible toward genotoxicity. In conclusion, the study suggests wide variation in enzyme activities and DNA damage due to polymorphisms in PON1 gene, which might have an important role in the identification of individual risk factors in workers occupationally exposed to OPs. © 2010 Elsevier Inc.


Grover M.,Immunization Technical Support Unit | Chauhan H.,Center for Epidemiology and Parasitic Diseases
Annals of Tropical Medicine and Public Health | Year: 2016

Background: The recent Ebola outbreak notified in West Africa recorded 6,553 cases and 3,083 deaths till 30th September 2014. This is the longest reported outbreak, suggesting poor preparedness and inadequate public health response. Learning from these experiences can help taking future disease-control measures in West Africa and elsewhere. Materials and Methods: This scoping study was done to summarize a range of evidences available on the current 'Ebola Viral Disease' (EVD) outbreak. All articles in English language related to the epidemiology of Ebola in humans, published between 1st March and 30th September 2014, were considered for review. Search engines, such as PubMed and Google Scholar, were used to search for the following keywords: 'Ebola,' 'Ebola Virus,' 'Ebola Viral Disease,' and 'Ebola Hemorrhagic Fever.' Snowballing using cross-references was done to find related literature on EVD. Related websites, blogs, and published news articles were reviewed. Studies of varying designs were considered without any quality assessment. Results: This is the first ever Ebola outbreak affecting large urban communities. Factors that worsened the outbreak were as follows: Weak health systems, unfavorable cultural practices, poverty, illiteracy, mistrust for the government, extensive cross-border movement, slow response from international agencies, and lack of tested treatment and prevention strategies. Simple measures of universal precaution, isolation and tracking of contacts, supportive treatment, and appropriate burial practices were difficult to implement. Conclusions: The outbreak in West Africa illustrates serious weaknesses in the ability of the international communities to respond to these outbreaks. Cost of setting up an infrastructure for early effective response is insignificant compared to the huge social and economic cost of the outbreak. Strong health system, improved preparedness, and effective community participation are imperative for control. © 2016 Annals of Tropical Medicine and Public Health | Published by Wolters Kluwer - Medknow.


Singh S.,National Center for Disease Control | Kumar V.,National Center for Disease Control | Kumar V.,IMS Engineering College | Singh P.,National Center for Disease Control | And 8 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

Previous studies have revealed that organophosphate pesticides (OPs) are primarily metabolized by xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticides-exposed workers. Present study was designed to determine the influence of CYP2C9, GSTM1, GSTT1 and NAT2 genetic polymorphisms on DNA damage in workers occupationally exposed to OPs. We examined 268 subjects including 134 workers occupationally exposed to OPs and an equal number of normal healthy controls. The DNA damage was evaluated using alkaline comet assay and genotyping was done using individual polymerase chain reaction (PCR) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Acetylcholinesterase and paraoxonase activity were found to be significantly lowered in workers as compared to control subjects which were analyzed as biomarkers of toxicity due to OPs exposure (p< 0.001). Workers showed significantly higher DNA tail moment (TM) compared to control subjects (14.32 ± 2.17 vs. 6.24 ± 1.37 tail % DNA, p< 0.001). GSTM1 null genotype was found to influence DNA TM in workers (p< 0.05). DNA TM was also found to be increased with concomitant presence of NAT2 slow acetylation and CYP2C9 *3/. *3 or GSTM1 null genotypes (p< 0.05). DNA TM was found increased in NAT2 slow acetylators with mild and heavy smoking habits in control subjects and workers, respectively (p< 0.05). The results of this study suggest that GSTM1 null genotypes, and an association of NAT2 slow acetylation genotypes with CYP2C9 *3/. *3 or GSTM1 null genotypes may modulate DNA damage in workers occupationally exposed to OPs. © 2011 Elsevier B.V.


Singh S.,National Center for Disease Control | Kumar V.,University of Delhi | Singh P.,National Center for Disease Control | Thakur S.,National Center for Disease Control | And 9 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2011

GSTM1, T1 and P1 are important enzymes of glutathione S-transferases (GSTs), involved in the metabolism of many endogenous and exogenous compounds. Individual genetic variation in these metabolizing enzymes may influence the metabolism of their substrates. The present study was designed to determine the genotoxic effects using DNA damage and its association with GSTM1, GSTT1, and GSTP1 (Ile105Val) genetic polymorphisms in workers occupationally exposed to organophosphate pesticides (OPs). We examined 230 subjects including 115 workers occupationally exposed to OPs and an equal number of normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using individual PCR or PCR-RFLP. Significantly higher DNA tail moment (TM) was observed in workers as compared to control subjects (14.41 ± 2.25 vs. 6.36 ± 1.41 tail % DNA, p< 0.001). The results revealed significantly higher DNA TM in workers with GSTM1 null genotype than those with GSTM1 positive (15.18 vs. 14.15 tail % DNA, p= 0.03). A significantly higher DNA TM was also observed in workers with homozygous Ile-Ile GSTP1 genotype than heterozygous (Ile-Val) and mutant (Val-Val) GSTP1 genotype (p= 0.02). In conclusion, the results show that null deletion of GSTM1 and homozygote wild GSTP1 genotype could be related to inter-individual differences in DNA damage arises from the gene-environment interactions in workers occupationally exposed to OPs. © 2011 Elsevier B.V.


Singh S.,National Center for Disease Control Formerly | Kumar V.,University of Delhi | Thakur S.,National Center for Disease Control Formerly | Banerjee B.D.,University of Delhi | And 9 more authors.
Environmental Toxicology and Pharmacology | Year: 2011

The present study was designed to evaluate genotoxicity, acetyl cholinesterase (AChE) activity, hepatic and renal toxicity in occupational workers exposed to mixture of pesticides (n = 70) with same number of healthy subjects as controls. The mean comet tail DNA % (TD %) and tail moment (TM) were used to measure DNA damage, while AChE activity and other biochemical parameters such as markers of nephrotoxicity (urea and creatinine) and hepatotoxicity (AST, ALT and ALP) were measured as biomarkers for toxicity due to exposure of pesticides. The occupational workers were continuously exposed to mixture of pirimiphos methyl, chlorpyrifos, temephos and malathion on a regular interval as per usage and activity. The comet assay using lymphocytes of exposed workers showed significantly higher TD percentage value (60.43% vs. 31.86%, p< 0.001) and TM value (14.48 μm vs. 6.42 μm, p< 0.001) in occupational workers as compared to controls. AChE activity in erythrocytes was found to be decreased (3.45. KAU/L vs. 9.55. KAU/L in controls, p< 0.001) and associated with the duration of exposure to pesticides used by the workers. Enzyme levels for hepatic and renal functions were also found significantly different in occupational workers than healthy controls (p< 0.001). These results suggest that the exposure to mixture of pirimiphos methyl, chlorpyrifos, temephos and malathion may induce DNA damage, decrease in AChE activity, hepatotoxicity as well as nephrotoxicity. Periodic biomonitoring of these biomarkers along with imparting education and training to occupational workers for safe application of pesticides is recommended for its potential hazards. © 2010 Elsevier B.V.

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