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KMID : 0379520050210040339
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한국독성학회지
2005 Volume.21 No. 4 p.339 ~ p.345
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DNA Adduct Formation and Expression of Ras Gene in the Liver of Rats Treated with Aflatoxins at Various Levels
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Kim Tae-Myung
Hue Jin-Joo
Li Lan
Kim Dae-Joong
Nam Sang-Yoon
Yun Young-Won
Lee Beom-Jun
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Abstract
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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.
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KEYWORD
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Aflatoxins, 8-Hydroxydeoxyguanosine (8-OxodG), Ras, Hepatotoxicity, Biomarker
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