CYP450 1A1 and p53 expression and DNA adduct formation in the liver of rats treated with a single dose of aflatoxins

아플라톡신을 간회 투여한 랫드의 간에서 CYP450 1A1, p53의 발현과 DNA adduct의 형성

  • Lee, Beom Jun (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Lee, Sook Jin (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Tae Myoung (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Dae Joong (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Nam, Sang Yoon (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Hyun, Sang Hwan (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Kang, Jong Koo (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Hong, Jin Tae (College of Pharmacy and Research Institute of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Cheul Kyu (National Institute of Toxicological Research, Korea FDA) ;
  • Yun, Young Won (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
  • 이범준 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 이숙진 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 김태명 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 김대중 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 남상윤 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 현상환 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 강종구 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 홍진태 (충북대학교 약학대학 및 동물의학연구소) ;
  • 김철규 (국립독성연구원 독성연구부) ;
  • 윤영원 (충북대학교 수의과대학 및 동물의학연구소)
  • Accepted : 2004.11.20
  • Published : 2004.12.30

Abstract

Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.

Acknowledgement

Supported by : 충북대학교

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