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KMID : 0603520000050010024
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Journal of Korean Association of Cancer Prevention
2000 Volume.5 No. 1 p.24 ~ p.30
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Effects of All-trans Retinoic Acid Supplementation on Rat Liver Hepatocarcinogenesis
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Lee Mi-Sook
Lee Min-Jae
Jang Ja-June
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Abstract
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Various liver diseases are associated with changes in retinoic acid metabolism and storage. These observations have led to speculation about whether retinoic acid level has an impact on hepatocacarcinogenesis. In this study we have investigated the porential roles of retinoic acid in the preneoplastic stage of diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. In addition, we also determined the relationship between retinoic acid supplementation and cell cycle-related proteins such as cyclin D1, cyclin E, CDK4, and p21. Three-week old female Sprague-Daeley rats were divided in two groups and DEN (50 ㎎/㎏) was injected intraperitoneally twice in 1 week. And then, all rats received 0.5㎎/㎏ carbon tetrachloride (CCl4) injection for 4 weeks. Phenobarbital was also treated during 10 weeks, after (CCl4) injection. In test group, 0.0012% all-trans retinoic acid was added to the AIN 76diet and treated during the experimental period. All animals were sacrificed 10 weeks after (CCl4) treatment. The results show that retinoic acid supplementation increases in glutathione-s-transferase placental form positive (GST-P+) foci number and area compared with control group. Proliferating cell nuclear antigen index was also increased by retinoic acid supplementation. However, liver collagen contents and cell cycle related proteins such as cyclin D1, cyclin E, CDK4, and p21 do not changed. These results demonstrate that retinoic acid may have promoting effect on DEN induced rat hepatocarcinogenesis. Additional studies are needed to understand the mechanism of the promoting effect.
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KEYWORD
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All-trans retinoic acid, Hepatocarcinogenesis, GST-P+ foci
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