Korean Journal of Veterinary Research 2004;44(4):507-513.
CYP450 1A1 and p53 expression and DNA adduct formation in the liver of rats treated with a single dose of aflatoxins
Beom Jun Lee1, Sook Jin Lee1, Tae Myoung Kim1, Dae Joong Kim1, Sang Yoon Nam1, Sang Hwan Hyun1, Jong Koo Kang1, Jin Tae Hong2, Cheul Kyu Kim3, Young Won Yun1
1College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University
2College of Pharmacy and Research Institute of Veterinary Medicine, Chungbuk National University
3National Institute of Toxicological Research, Korea FDA
아플라톡신을 간회 투여한 랫드의 간에서 CYP450 1A1, p53의 발현과 DNA adduct의 형성
이범준1, 이숙진1, 김태명1, 김대중1, 남상윤1, 현상환1, 강종구1, 홍진태2, 김철규3, 윤영원1
1충북대학교 수의과대학 및 동물의학연구소
2충북대학교 약학대학 및 동물의학연구소
3국립독성연구원 독성연구부
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.
Key Words: aflatoxins, CYP450 1A1, p53, Glutathione-S-transferase placental form (GST-P), 8-Hydroxydeoxyguanosine (8-OxodG)
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