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Journal of Preventive Medicine and Public Health 2005;38(3): 345-350.
Effects of Oxidative DNA Damage Induced by Polycyclic Aromatic Hydrocarbons and Genetic Polymorphism of the Paraoxonase-1 (PON1) Gene on Lung Cancer.
Chul Ho Lee, Kye Young Lee, Kang Hyeon Choe, Yun Chul Hong, Yong Dae Kim, Jong Won Kang, Heon Kim
1Department of Preventive Medicine, College of Medicine, Chungbuk National University, Korea. kimheon@cbu.ac.kr
2Department of Internal Medicine, Dankook University College of Medicine, Korea.
3Department of Internal Medicine, College of Medicine, Chungbuk National University, Korea.
4Department of Preventive Medicine, Seoul National University College of Medicine, Korea.
5Department of Preventive Medicine, Seoul National University, Institute of Environmental Medicine, SNUMRC, Korea.
ABSTRACT
OBJECTIVE: Polycyclic aromatic hydrocarbons (PAHs), which are risk factors for lung cancer, have been reported to induce oxidative DNA damage. The paraoxonase (PON) plays a significant role in the detoxification of a variety of organophosphorous compounds, with paraoxonase-1 (PON1) being one of the endogenous free-radical scavenging systems in the human body. The aim of this case-control study was to investigate the effects of PAH exposure, oxidative stress and the Q192R polymorphism of PON1 genes, and their interactions in the carcinogenesis of lung cancer. METHODS: One hundred and seventy seven lung cancer patients and 177 age- and sex-matched controls were enrolled in this study. Each subject was asked to complete a questionnaire concerning their smoking habits and environmental exposure to PAHs. The Q192R genotypes of the PON1 gene was examined, and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8- hydroxydeoxyguanosine (8-OH-dG) measured. RESULTS: Cigarette smoking was found to be a significant risk factor for lung cancer. The urinary 8-OH-dG level was higher in the patients, whereas the urinary 1-OHP and 2- naphthol levels were higher in the controls. There was a significant correlation between the urinary levels of 8-OHdG and 1-OHP in both the cases and controls. The PON1 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Q/Q genotype of the PON1 gene were found to be at higher risk of developing lung cancer. There was a significant correlation between the urinary levels of 8-OH-dG and 1-OHP in those with the PON1 Q/Q genotype. CONCLUSIONS: These results lead to the conclusion that PAHs would induce oxidative DNA damage, especially in individuals with the PON1 Q/Q genotype. Therefore, people with the PON1 Q/Q genotype would be more susceptible to lung cancer than those with the R/R or Q/R genotypes of the PON1 gene.
Key words: Lung cancer; Paraoxonase-1; 8-hydroxydeoxyguanosine; Polycyclic aromatic hydrocarbons
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