Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Effect of ALDH2 Enzyme Activity on the Level of 8-Hydroxydeoxyguanosine in Tissues Following Ethanol Exposure

ALDH2 효소의 활성이 알코올 섭취에 의한 8-hydroxydeoxyguanosine의 장기별 농도에 미치는 영향

  • Zhang, Yan Wei (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Choi, Sheung-Hee (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Kim, Yun-Sik (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Moon, Sun-In (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Eom, Sang-Yong (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Kim, Yong-Dae (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Kim, Heon (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University)
  • 장연위 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 최승희 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 김윤식 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 문선인 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 엄상용 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 김용대 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 김헌 (충북대학교 의과대학 예방의학교실 및 의학연구소)
  • Published : 2008.08.30
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Abstract

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.

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.

Keywords

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