Retinol and β-Carotene Concentrations in Skin, Papillomas and Carcinomas, Liver, and Serum of Mice Fed Retinoic Acid or β-Carotene to Suppress Skin Tumor Formation

Carol S. Jones, Li Chuan Chen, Theresa Ben, Michelle Brugh-Collins, Ulrike Lichti, Luigi M. De Luca

Research output: Contribution to journalArticle

Abstract

Using 7, 12-dimethylbenz[a] anthracene as the initiator and 12-O-tetradecanoyl-13-acetate as the tumor promoter on the dorsal skin of Senear mice, we previously showed that pharmacological dietary all-Xrzns-retinoic acid and p-carotene inhibit the conversion of papillomas to carcinomas in a two-stage system of chemical carcinogenesis. The purpose of this study was to determine the influence of dietary retinoic acid and p-carotene on retinoid and p-carotene concentrations in skin and other tissues. We were unable to measure tissue retinoic acid because of the relatively limited amount of tissue available for analysis and the fast rate of metabolism. Different dietary levels of retinoic acid or pcarotene did not influence total retinol of skin, papilloma, and carcinoma tissues, which all showed a concentration of approximately 1 ±0.5 μg/g wet wt. Equally refractory to dietary retinoic acid or p-carotene was serum retinol concentration. In contrast, dietary retinoic acid protected loss of liver retinol and retinyl palmitate, and p-carotene caused an increase in p-carotene and retinyl palmitate in liver but did not affect serum and liver retinol. We further investigated metabolic and functional aspects of retinoic acid in cultured mouse epidermal keratinocytes (LC-8 cells) and found that these cells actively metabolized [10, 1 l-lACJretinoic acid to polar compounds. Isomers of retinoic acid were a minor product in the presence of cells and the major product when incubated in serum-containing medium in the absence of cells. From the functional point of view, exposure of LC-8 cells to 3 × ICt6M all-lvans-retinoic acid (RA) caused a 75-fold induction in tissue transglutaminase and an approximately 9-fold induction in KL6M RA at three days of culture. We conclude that retinoic acid spares endogenous retinol and that p-carotene greatly enhances liver retinyl palmitate levels. Moreover we show that although mouse epidermal cells metabolize retinoic acid at a very high rate, they respond functionally by induction of tissue transglutaminase activity. Because this enzyme has been suggested to be involved in programmed cell death, we are presently investigating the possibility that it may be involved in the inhibition of carcinogenesis in mice fed pharmacological doses of RA.

Original languageEnglish (US)
Pages (from-to)83-93
Number of pages11
JournalNutrition and Cancer
Volume21
Issue number1
DOIs
StatePublished - Jan 1994
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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