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Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids).
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1976
Year
Natural RetinoidsSynthetic AnalogsHealth SciencesOncogenic AgentMedicinePhotocarcinogenesisChemoprevention StrategyChemical CarcinogenesisCancer PreventionCell ProliferationCell DifferentiationSynthetic RetinoidsPharmacologyRadiation OncologyTumor MicroenvironmentCancer ResearchOxidative StressVitamin A
Vitamin A and synthetic retinoids regulate epithelial cell differentiation, and future human chemoprevention will rely on further molecular modifications. The study describes an approach to chemoprevention of common epithelial cancers during the preneoplastic phase. Retinoid effects on cell differentiation are assessed in organ culture, and structural modifications of the retinoid core enhance potency while reducing toxicity. In animals, dietary retinoid deficiency increases carcinogenesis risk, while high‑dose natural retinoids modestly prevent it but are limited by distribution and toxicity; synthetic retinoids, however, are more potent and less toxic, improving prevention.
An approach to chemoprevention of common forms of epithelial cancer, during the period of preneoplasia, is described. Vitamin A and its synthetic analogs (retinoids) are potent agents for control of cell differentiation in many epithelial tissues. Direct effects of retinoids on normal and preneoplastic cell differentiation can be measured in organ culture. In experimental animals, deficiency of dietary retinoids enhances susceptibility to chemical carcinogenesis. Natural retinoids, fed at high dietary levels, have some ability to prevent chemical carcinogenesis in epithelial tissues of bronchi, trachea, stomach, uterus, and skin of experimental animals. However, natural retinoids have limited usefulness for chemoprevention of cancer because of inadequate tissue distribution and excessive toxicity. Synthetic retinoids have been made and shown to be more potent and less toxic for prevention of cancer in animals. Several structural modifications of the ring and terminal portions of the retinoid molecule have significant biological activity; modification of the side chain has been more difficult. The potential future usefulness of this approach to cancer prevention in man will depend on further synthetic modification of the retinoid molecule.