title: 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 μm/cell, P < 0.01) or low pesticide exposure (2.18 μm/cell, P < 0.01) had a significantly greater DNA tail moment than controls (1.28 μm/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 μm/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.
authors.affiliation: Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan ; Department of Occupational Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan ; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Chun-Huang
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan ; Department of Pharmacy, Taipei Medical University, Wan Fang Hospital, Taipei 110, Taiwan.
authors.forename: Man-Tzu Marcie
authors.initials: MT
authors.lastname: Wu
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Chia-Hsuan
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Tzu-Yen
authors.initials: TY
authors.lastname: Tseng
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Chang
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Ying-Ti
authors.initials: YT
authors.lastname: Li
authors.affiliation: Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan ; Department of Occupational Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: School of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Tsung-Shing
authors.initials: TS
authors.lastname: Wang
authors.affiliation: Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan ; Department of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Ruey-Hong
authors.identifier: 0000-0002-1337-7275
authors.initials: RH
authors.lastname: Wong
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000383:Agriculture; D016022:Case-Control Studies; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis*; D010575:Pesticides / Q000633:toxicity*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010575:Pesticides