http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
ALDH2 효소의 활성이 알코올 섭취에 의한 8-hydroxydeoxyguanosine의 장기별 농도에 미치는 영향
장연위(Yan Wei Zhang),최승희(Sheung-Hee Choi),김윤식(Yun-Sik Kim),문선인(Sun-In Moon),엄상용(Sang-Yong Eom),김용대(Yong-Dae Kim),김헌(Heon Kim) 한국생명과학회 2008 생명과학회지 Vol.18 No.8
본 연구에서는 ALDH2 knockout 마우스를 이용하여 에탄올을 경구 투여한 후 간조직 및 뇌조직, 그리고 폐조직에서의 8-hydroxydeoxyguanosine (8-OHdG) 농도를 측정하여 각 장기에서의 산화적 유전자 손상정도를 평가하고 ALDH2 효소활성과의 관련성을 파악하였다. 간조직의 8-OHdG 농도는 에탄올 투여에 의해서도 유의하게 증가하지만 ALDH2 효소의 결핍이 더욱 큰 영향을 주는 것으로 확인되었다. 또한, 뇌조직과 폐조직의 8-OHdG 농도도 에탄올에 의해 모두 유의하게 증가하는 것으로 나타났으며 폐조직에서의 8-OHdG 농도는 ALDH2 효소의 활성에 따라 유의하게 영향을 받는 것으로 나타났다. 본 연구에서 에탄올의 반복적인 투여는 간조직 뿐 아니라 뇌조직과 폐조직에서도 산화적 유전자 손상을 유발하는 것으로 확인되었으며, 적어도 에탄올에 의한 간조직과 폐조직에서의 산화적 유전자 손상은 ALDH2 활성이 결핍된 경우에 더욱 커지는 것으로 조사되었다. 본 연구의 결과는 ALDH2 효소가 결핍된 사람에서 각종 암발생 위험도가 크게 나타나는 이유를 규명하는데 매우 중요한 근거자료로 활용될 수 있을 것으로 기대된다. Individuals who regularly consume excessive quantities of alcohol are at a greater risk of developing various cancers such as esophageal, pharyngeal and lung cancers compared to normal populations if they are deficient in ALDH2 enzyme activity. We evaluated oxidative DNA damage in the liver, brain, and lung tissues of Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. The 8-hydroxydeoxyguanosine (8-OHdG) level in each tissue was evaluated as a biomarker of oxidative DNA damage. The 8-OHdG level in the liver, brain, and lung tissues was significantly increased following ethanol treatment. In addition, the level of 8-OHdG in the liver and lung tissues was affected by ALDH2 enzyme activity. This result suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated diseases, including cancer.
GPX1 및 hOGG1 유전자다형성에 따른 유전자의 산화적 손상 및 폐암 발생 위험도 평가
이철호,이계영,최강현,홍윤철,노성일,엄상용,고영준,장연위,임동혁,강종원,김헌,김용대,Lee, Chul-Ho,Lee, Kye-Young,Choe, Kang-Hyeon,Hong, Yun-Chul,Noh, Sung-Il,Eom, Sang-Yong,Ko, Young-Jun,Zhang, Yan-Wei,Yim, Dong-Hyuk,Kang, Jong-Won,Kim, H 대한예방의학회 2006 예방의학회지 Vol.39 No.2
Objectives : Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer. Methods : Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. Results : Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p<0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR=2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage. Conclusions : These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.