OGG1 Genetic Polymorphism is Associated with Mitochondrial DNA Damage in Pesticide-Exposed Fruit Growers

• Main Authors: Pei-Lin Huang, 黃佩琳
• Other Authors: Jim-Shoung Lai
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/50240000042238510758

碩士 === 中國醫藥大學 === 職業安全衛生學系碩士班 === 95 === Pesticide exposure has been observed to be associated with various neoplastic diseases in previous epidemiological studies. Oxidative damage to mitochondrial DNA (mtDNA) has been also proposed to be an important mediator in cell death and carcinogenesis. In mitochondria, the manganese superoxide dismutase (MnSOD) is the first line of defense against superoxide radicals. The 8-oxoguanine DNA glycosylase (OGG1) is also the major DNA glycosylase for the repair of 8-oxoG lesions in the mitochondrial DNA. However, the mitochondrial genotoxicity of pesticides in people with various genetic variation of human MnSOD and OGG1 has not been investigated. In this study, the mtDNA (ND1 gene) and nuclear DNA (β-actin gene) in the peripheral blood of 120 fruit growers who experienced pesticide exposure and 106 unexposed controls was quantified by real-time quantitative polymerase chain reaction (real time qPCR). To evaluate mitochondrial DNA damage, mitochondrial to nuclear DNA ratio was calculated by dividing the mtDNA quantity for ND1 gene by the corresponding β-actin quantity. Questionnaires were administered to obtain demographic data, and histories of cigarette-smoking habits, and occupation. The genotypes of MnSOD and OGG1 were identified by the PCR based restriction fragment length polymorphism (RFLP). The results showed that subjects experiencing high or low pesticide exposure had a greater mtDNA content (mtDNA damage) than did controls. Interestingly, after adjusting the effect of possible cofounders, the multiple regression model revealed that OGG1 Ser-Ser (P = 0.03) genotype was significantly associated with an increased relative content of mtDNA. However, no significant association between MnSOD genotype and mtDNA damage was revealed. Thus, results suggest that individuals with susceptible OGG1 genotype may experience an increased risk of mitochondrial DNA damage by pesticide exposure.