Biochemical Mechanism of Modulation of Skin Carcinogenesis by Retinoids

Abstract

Vitamin A acid (retinoic acid), a major metabolite of retinol or retinyl esters (8, 11, 16), is required to maintain normal growth and differentiation of epithelial tissues (54, 58), but it cannot replace retinal to support the visual function and reproduction (15, 19). Epidemiological study and evidence from experimental animals indicate a close association between retinoic acid deficiency and enhanced susceptibility to chemical carcinogenesis of the respiratory system, bladder, and colon (30, 42). Retinoic acid has been used in experimental animals to prevent and treat cancers of a variety of epithelial tissues (bronchi and trachea, stomach, intestine, uterus, kidney and bladder, testis, prostate, pancreatic ducts, and skin), the target sites of the origin of cancer (3, 26, 32, 42, 51). The pharmacological use of natural retinoids in chemoprevention of cancer is handicapped by their toxic effects (hypervitaminosis syndromes) (3). Recently, a number of retinoids have been synthesized in an attempt to obtain compounds with less host toxicity and with greater antitumorigenicity, which have been found to be superior in the prevention of cancer of skin, lung, bladder, and breast in animals (3, 33, 41). In addition, retinoids have therapeutic effects in skin diseases such as acne, psoriasis, and ichthyosis (1, 35). Retinoids reverse carcinogen-induced lesions in tissue culture (13, 28) and influence the growth of tumor cell lines (24).