Author: Dawson, M.I.

Source: Current Pharmaceutical Design, Volume 6, Number 3, 1 February 2000 , pp. 311-325(15)

Publisher: Bentham Science Publishers

Abstract:

Preformed vitamin A (all-trans-retinol and its esters) and provitamin A (beta-carotene) are essential dietary nutrients that provide a source of retinol. Both retinyl esters and beta-carotene are metabolized to retinol. The retinol-binding proteins on binding retinol provide a means for solubilizing retinol for delivery to target tissues and for regulating retinol plasma concentrations. Oxidation of retinol provides retinal, which is essential for vision, and retinoic acid, a transcription factor ligand that has important roles in regulating genes involved in cell morphogenesis, differentiation, and proliferation. The observations that vitamin A can produce cell and tissue changes similar to those found during neoplastic transformation and that vitamin supplementation can reverse this process indicated a potential role for vitamin A in cancer prevention. Thus far, correlative epidemiological studies on vitamin A use and cancer prevention have produced mixed results, as this review indicates. Apparently, in populations deficient in vitamin A (caused by an inadequate diet or tobacco use), supplementation programs appear to be effective in reducing cancer incidence. In groups already having sufficient dietary or supplemental vitamin A, cancer prevention by added vitamin A may not be particularly effective. The most likely reason for the low efficacy in the latter groups is that feedback mechanisms that increase retinol storage in the liver limit retinol plasma levels whereas, supplementation at higher doses causes toxicity. In addition to serving as a metabolic source of retinol, beta-carotene, along with other dietary carotenoids, function as antioxidants that can prevent carcinogenesis by decreasing the levels of the free-radicals that cause DNA damage.

Keywords: vitamin A; nutrition; all trans retinol; cancer; dietary sources; absorption; biosynthesis; transport; 3 4 3 4 tetrachlorobiphenyl TCBP; interstitial retinol binding protein IRBP; CRBP I; retinoid X receptors; RXR; CRBP I gene; glucocrticoid dexamethasone decreases CRBP I; dihydroxyvitamin D3; Holo CRBP I; lecithin retinol transferase LRAT; Apo CRBP; CRBP II; CRBPs; vitamin A deficiency Hypovitaminosis A; Carotenoids; Hypercarotenemia; Cancer Prevention; carcinogenesis; retinoid X receptor; TTR transthyretin; ARAT acyl CoA; Vitamin A absorption; lycopene; carotene

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612003401190

Publication date: 2000-02-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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