Increase in Liver Ornithine Decarboxylase Activity Associated with the Enhancement of N-nitrosomorpholine Rat Hepatocarcinogenesis Induced by a Low-Vitamin A Diet

Miyako Baba*†, Masaharu Tatsuta* and Tadao Itoh†

*Department of Gastrointestinal Oncology, The Center for Adult Diseses, Osaka 537 and †Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago 683, Japan

We investigated the effects of a low-vitamin A diet on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and on ornithine decarboxylase (ODC) activity in the liver and the labeling index of hepatic lesions in male S prague-Dawley rats. The rats were fed on a low-vitamin A diet from the beginning of the experiment, and given drinking water containing NNM from week 2 for 8 weeks. The rats were killed at weeks 9, 13 and 16. Quantitative histological analyses showed that a low-vitamin A diet significantly increased the size but not the number of placental glutathione-S-transferase (GST-P)-positive hepatic lesions from week 9 and of gamma-glutamyl transpeptidase (GGT)-positive hepatic lesions from week 13. A Iow-vitamin A diet also significantly increased the percentage of volume of hepatocellular carcinomas in the liver in week 16. In addition, it greatly increased ODC activity in the liver tissue and the labeling index of preneoplastic lesions, but did not increase the labeling index of hepatocytes adjacent to the hepatic lesions or that of hepatocellular carcinomas. These findings indicate that a low-vitamin A diet enhances hepatocarcinogenesis, and suggest that this enhancement of hepatocarcinogenesis by a low-vitamin A diet is due to increases the labeling index of pre-neoplastic lesions and its subsequent enhancement of the development of hepatocellular carcinomas from the pre-neoplastic lesions.

Key words: Bromodeoxyuridine; gamma-glutamyl transpeptidase; N-nitrosomorpholine; ornithine decarboxylase; placental glutathione-s-transferase

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