Abstract
The goal of research into retinoic acid is to maintain or improve the pharmacologic activities of topically applied retinoic acid while decreasing both local and systemic toxicity and improving chemical stability. Data are presented from a wide range of in vitro and in vivo test systems for retinoic acid, its congeners such as etretinate, and recently synthesized derivatives. The in vitro tests involved cell culture and biochemical assays: rat testes cytosol (receptor binding), mouse embryo teratocarcinoma cells (morphologic evaluation of differentiation), transformed human keratinocytes (cross-linked envelope formation), and polymorphonuclear leukocytes (lipoxygenase enzyme). The in vivo tests were carried out in the hairless rat (ornithine decarboxylase inhibition), the rabbit (irritation), and the guinea pig (ultraviolet erythema). Results from these experiments were used to determine biologic indices for the test substances. Subsequently, these test systems were used to evaluate a series of new compounds designed to control the chemical nature of a key double bond in the retinoic acid structure. Results are presented to show that different actions on the proliferative, differentiating, and inflammatory processes can be obtained by progressive aromatization of the retinoic acid structure.
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