Polymorphisms in metabolic GSTP1 and DNA-repair XRCC1 genes with an increased risk of DNA damage in pesticide-exposed fruit growers.
Pesticide exposure is associated with various neoplastic diseases and congenital malformations. Previous studies have indicated that pesticides may be metabolized by cytochrome P450 3A5 or glutathione S-transferases. DNA-repair genes, including X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD), may also be implicated in the process of pesticide-related carcinogenesis. Thus, we investigated whether various metabolic and DNA-repair genotypes increase the risk of DNA damage in pesticide-exposed fruit growers. Using the comet assay, the extent of DNA damage was evaluated in the peripheral blood of 135 pesticide-exposed fruit growers and 106 unexposed controls. The metabolic genotypes CYP3A5 (A(-44)G) and GSTP1 (Ile105Val) and DNA-repair genotypes XRCC1 (Arg399Gln, Arg194Trp, T(-77)C) and XPD (Asp312Asn, Lys751Gln) were identified by polymerase chain reaction. Our multiple regression model for DNA tail moment showed that age, high pesticide exposure, low pesticide exposure, GSTP1 Ile-Ile, and XRCC1 399 Arg-Arg genotype were associated with increased DNA tail moment (DNA damage). Further analysis of interaction between GSTP1 and XRCC1 genes that increase susceptibility revealed a significant difference in DNA tail moment for high pesticide-exposed subjects carrying both GSTP1 Ile-Ile with XRCC1 399 Arg-Arg genotypes (2.49+/-0.09 microm/cell; P=0.004), compared to those carrying GSTP1 Ile-Val/Val-Val with XRCC1 399 Arg-Gln/Gln-Gln genotypes (1.98+/-0.15 microm/cell). These results suggest that individuals with susceptible metabolic GSTP1 and DNA-repair XRCC1 genotypes may be at increased risk of DNA damage due to pesticide exposure.
Wong
Ruey-Hong
RH
Department of Public Health, College of Health Care and Management, Chung Shan Medical University, No. 110 Chien-Kuo N. Road, Sec. 1, Taichung 40242, Taiwan. rueyhong@csmu.edu.tw
Chang
Shu-Yuan
SY
Ho
Shu-Wei
SW
Huang
Pei-Lin
PL
Liu
Yi-Jie
YJ
Chen
Yu-Ching
YC
Yeh
Yu-Hsuan
YH
Lee
Hong-Shen
HS
D020552:Comet Assay; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005638:Fruit; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D010575:Pesticides / Q000633:toxicity*; D011110:Polymorphism, Genetic; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D010575:Pesticides; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051549:Glutathione S-Transferase pi