Toxicological Research

  • 제21권4호
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  • Pages.339-345
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  • 2005
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지

랫드의 간에서 다양한 농도의 아플라톡신 투여에 의한 DNA Adduct의 형성과 Ras의 발현양상

DNA Adduct Formation and Expression of Ras Gene in the Liver of Rats Treated with Aflatoxins at Various Levels

  • 김태명 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 허진주 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 리란 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 김대중 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 남상윤 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 윤영원 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 이범준 (충북대학교 수의과대학 및 동물의학연구소)
  • Kim Tae Myoung (College of Veterinary Medicine and Research Institute of Veterinary Medicine) ;
  • Hue Jin Joo (College of Veterinary Medicine and Research Institute of Veterinary Medicine) ;
  • Li Lan (College of Veterinary Medicine and Research Institute of Veterinary Medicine) ;
  • Kim Dae Joong (College of Veterinary Medicine and Research Institute of Veterinary Medicine) ;
  • Nam Sang Yoon (College of Veterinary Medicine and Research Institute of Veterinary Medicine) ;
  • Yun Young Won (College of Veterinary Medicine and Research Institute of Veterinary Medicine) ;
  • Lee Beom Jun (College of Veterinary Medicine and Research Institute of Veterinary Medicine)
  • 발행 : 2005.12.01
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초록

Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin $B_1\;(AFB_1)$ is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types $(AFB_2,\;AFG_1\;and\;AFG_2)$ of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1,\;AFB_2,\;AFG_1\;and\;AFG_2$ at the dose of 250, 1250, and $2500\;{\mu}g/kg$ body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of $AFB_1\;and\;AFG_1$ was significantly low. The treatment of $AFB_1$ at the high dose of $2500\;{\mu}g/kg$ showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by $AFB_2\;AFG_1,\;and\;AFG_2$ were not clearly found. 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 the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by $AFB_1$ at the dose of $1250\;{\mu}g/kg$ was increased twice compared to the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ at all doses decreased the expression of ras in the liver. 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 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to $AFB_1$ in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.

키워드

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