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Chemoprevention of Tumor Development and Metastasis of Transplantable Hepatocellular Carcinomas in Rats by Vitamin A^1,2,

Dorothy M. Morré^*, Thomas M. Kloppel^3,, Ann L. Rosenthal^* and Paula C. Fink

^* Department of Foods and Nutrition Department of Biological Sciences, Purdue University, West Lafayette, IN 47907

Vitamin A is attracting increasing attention as a potential cancer chemopreventative agent. To investigate the effect of vitamin A on tumor establishment, growth and metastasis, rats were fed diets containing zero, adequate or excess (100X adequate) amounts of vitamin A prior to subcutaneous injection with transplantable hepatocellular carcinomas derived from solid tumors induced by N-2-fluorenylacetamide. When rats were injected at the same time the dietary regimen was begun, tumor growth was similar in both the deficient and adequate vitamin A groups with 20% less in the excess vitamin A group. However, when rats were injected 2 weeks post-initiation of the dietary regimen, tumors were fewer and appeared later under conditions of either vitamin A deficiency or excess. When rats were injected with a metastatic line 2 weeks following initiation of the dietary regimen, no metastases were observed in the animals fed excess vitamin A, but 60% had metastases in the deficient group and 75% in the adequate group. Results suggest that dietary extremes of vitamin A affect tumor establishment and growth and excess amounts prevent metastasis of transplantable hepatomas in the rat.

KEY WORDS: • vitamin A • hepatocellular carcinoma • metastasis • chemoprevention

¹ Supported in part by Purdue Research Foundation, 8546-561264 Paper # 7878 of the Purdue University Agricultural Experiment Station, West Lafayette, IN 47907.

² Presented in part at the XIth International Congress of Biochemistry, Toronto, Ontario, July 1979.

³ Present address: Department of Medicine, National Jewish Hospital and Research Center, Denver, CO 80206.

Manuscript received 9 July 1979.