Document Detail

Oxidation of retinol to retinoic acid as a requirement for biological activity in mouse epidermis.
MedLine Citation:
PMID:  3191479     Owner:  NLM     Status:  MEDLINE    
The food and fragrance additive citral (3,7-dimethyl-2,6-octadienal) inhibits the oxidation of retinol to retinoic acid in mouse epidermis on local application. This inhibitory property was used to test the hypothesis that oxidation to retinoic acid is rate limiting for the biological activity of vitamin A (retinol) in epithelial tissues. Citral was tested as a modulator of the biological activities of retinol and retinoic acid using two bioassays performed in Skh/hr1 (hairless) mice: (a) the ability to induce epidermal hyperplasia; (b) the ability to inhibit the induction of epidermal ornithine decarboxylase activity by tumor promoters. Citral treatment inhibited the ability of retinol, but not of retinoic acid, to induce epidermal hyperplasia. Similarly, citral treatment decreased the ability of retinol, but not of retinoic acid, to inhibit the induction of epidermal ornithine decarboxylase activity by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Although citral had little effect on epidermal ornithine decarboxylase activity when applied alone, it potentiated the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate. The ability of citral to inhibit retinoic acid formation from retinol and the specificity of citral for inhibition of the biological activities of retinol but not retinoic acid are evidence that oxidation to retinoic acid is obligatory for the measured biological activities of retinol. Furthermore, the ability of citral to potentiate the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate suggests that modulation of the retinol oxidation pathway by such agents may enhance susceptibility to tumor promoters.
M J Connor
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  48     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1988 Dec 
Date Detail:
Created Date:  1989-01-09     Completed Date:  1989-01-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7038-40     Citation Subset:  IM    
Department of Medicine, UCLA School of Medicine 90024.
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MeSH Terms
Epidermis / drug effects,  metabolism*
Mice, Hairless
Ornithine Decarboxylase / antagonists & inhibitors
Terpenes / pharmacology
Tetradecanoylphorbol Acetate / pharmacology
Tretinoin / metabolism*
Vitamin A / metabolism*
Grant Support
Reg. No./Substance:
0/Monoterpenes; 0/Terpenes; 11103-57-4/Vitamin A; 16561-29-8/Tetradecanoylphorbol Acetate; 302-79-4/Tretinoin; 5392-40-5/citral; EC Decarboxylase

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