Dataset Information

Multidrug resistance 1 gene variants, pesticide exposure, and increased risk of DNA damage.

ABSTRACT: The P-glycoprotein, encoded by the multidrug resistance (MDR)1 gene, extrudes fat-soluble compounds to the extracellular environment. However, the DNA damage of pesticides in subjects with genetic variation in MDR1 has not been investigated. In this study, the comet assay was applied to examine the extent of DNA damage in the peripheral blood of 195 fruit growers who had been exposed to pesticides and 141 unexposed controls. The MDR1 polymorphisms were identified. Questionnaires were administered to obtain demographic data and occupational history. Results showed subjects experiencing high (2.14??m/cell, P < 0.01) or low pesticide exposure (2.18??m/cell, P < 0.01) had a significantly greater DNA tail moment than controls (1.28??m/cell). Compared to the MDR1 T-129C (rs3213619) TC/CC carriers, the TT carriers had increased DNA tail moment in controls (1.30 versus 1.12??m/cell, P < 0.01). Similar results were observed in the high and low pesticide-exposed groups. Combined analysis revealed that pesticide-exposed fruit growers with MDR1 -129 TT genotype had the greatest DNA damage in the subjects with the combinations of pesticide exposure and MDR1 -129 genotypes. In conclusion, pesticide exposed individuals with susceptible MDR1 -129 genotypes may experience increased risk of DNA damage.

SUBMITTER: Chen CC

PROVIDER: S-EPMC3984798 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Multidrug resistance 1 gene variants, pesticide exposure, and increased risk of DNA damage.

Chen Chun-Chieh CC Huang Chun-Huang CH Wu Man-Tzu Marcie MT Chou Chia-Hsuan CH Huang Chia-Chen CC Tseng Tzu-Yen TY Chang Fang-Yu FY Li Ying-Ti YT Tsai Chun-Cheng CC Wang Tsung-Shing TS Wong Ruey-Hong RH

BioMed research international 20140326

The P-glycoprotein, encoded by the multidrug resistance (MDR)1 gene, extrudes fat-soluble compounds to the extracellular environment. However, the DNA damage of pesticides in subjects with genetic variation in MDR1 has not been investigated. In this study, the comet assay was applied to examine the extent of DNA damage in the peripheral blood of 195 fruit growers who had been exposed to pesticides and 141 unexposed controls. The MDR1 polymorphisms were identified. Questionnaires were administere ...[more]

PMID: 24791009

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Project description:The intersectional risks of children in United States immigrant communities include environmental exposures. Pesticide exposures and their biological outcomes are not well characterized in this population group. We assessed pesticide exposure and related these exposures to DNA double-strand breaks (DSBs) in Latinx children from rural, farmworker families (FW; N = 30) and from urban, non-farmworker families (NFW; N = 15) living in North Carolina. DSBs were quantified in hair follicular cells by immunostaining of 53BP1, and exposure to 72 pesticides and pesticide degradation products were determined using silicone wristbands. Cholinesterase activity was measured in blood samples. DSB frequencies were higher in FW compared to NFW children. Seasonal effects were detected in the FW group, with highest DNA damage levels in April-June and lowest levels in October-November. Acetylcholinesterase depression had the same seasonality and correlated with follicular DNA damage. Organophosphate pesticides were more frequently detected in FW than in NFW children. Participants with organophosphate detections had increased follicular DNA damage compared to participants without organophosphate detection. Follicular DNA damage did not correlate with organochlorine or pyrethroid detections and was not associated with the total number of pesticides detected in the wristbands. These results point to rural disparities in pesticide exposures and their outcomes in children from vulnerable immigrant communities. They suggest that among the different classes of pesticides, organophosphates have the strongest genotoxic effects. Assessing pesticide exposures and their consequences at the individual level is key to environmental surveillance programs. To this end, the minimally invasive combined approach used here is particularly well suited for children.Supplementary informationThe online version contains supplementary material available at 10.1007/s12403-023-00609-1.

Project description:BACKGROUND:Organophosphates (OP) are widely used insecticides that acutely inhibit acetylcholinesterase enzyme activity. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to elucidate epigenetic changes associated with OP exposure, using untargeted analysis of genome-wide DNA methylation data. METHODS:In a population-based case control study of Parkinson's disease (PD), we assessed ambient OP exposure via residential and workplace proximity to commercial applications. We investigated associations between OP exposure and genome-wide DNA methylation (Illumina 450?k) in 580 blood samples (342 PD patients, 238 controls) and 259 saliva samples (128 patients, 131 controls). To identify differential methylation related to OP exposure, we controlled for age, sex, European ancestry, and PD status; in addition, we stratified by disease status. RESULTS:We identified 70 genome-wide significant CpGs, including cg01600516 in ALOX12 (cor?=?0.27, p?=?1.73E-11) and two CpGs in HLA genes, cg01655658 (cor?=?-0.24, p?=?2.80E-09) in HLA-L (pseudogene) and cg15680603 (cor?=?0.20, p?=?7.94E-07) in HLA-DPA1. Among the 70 CpGs located in 41 genes, 14 were also differentially methylated in saliva samples. The most overrepresented pathway was the nicotinic acetylcholine receptor signaling pathway (fold enrichment?=?15.63, p?=?1.01E-03, FDR?=?1.64E-01). Expanding to a larger number of genes (CpG p?<?5E-04, FDR?<?2.25E-01; 1077 CpGs, 662 genes), the most enriched pathway shifted to the muscarinic acetylcholine receptor 1 and 3 signaling pathway (p-value?=?5.36E-04, FDR?=?4.73E-02). When we stratified by PD status, results were similar. Of the 70 significant CpGs, 63 were detected among both patients and controls and 7 were only associated with OP exposure among patients. CONCLUSIONS:This study finds chronic low-level OP exposure is associated with differential DNA methylation in blood and saliva, both in elderly population controls and PD patients. Our study results suggest that long-term sub-acute OP exposure influences methylation in genes enriched for muscarinic and nicotinic acetylcholine receptor pathways.

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Multidrug resistance 1 gene variants, pesticide exposure, and increased risk of DNA damage.

Publications

Multidrug resistance 1 gene variants, pesticide exposure, and increased risk of DNA damage.

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