ABSTRACT
This chapter examines the ability of a variety of structurally modified retinoids to reverse keratinizing squamous metaplasia in vitamin A-deficient hamster tracheas in culture. Retinoic acid (RA) can be modified at the hydrophobic ring, the polyene side chain, or the polar terminus to reduce toxicity and alter tissue distribution, yet still maintain the ability to control normal epithelial cell differentiation. Methylnaphthalenecarboxylic acid analogs of retinoid were designed to assess the effect that methyl groups at positions corresponding to the 19- and 20-methyl groups of RA would have on activity. The importance of retinoids in chemoprevention of cancer received attention with the findings that retinoids can prevent cancer of the bladder, lung, and skin in experimental animals and suppress in vitro expression of malignant transformation. The standard hamster tracheal organ culture (TOC) assay permits measurement of the ability of biologically active retinoids to reverse keratinisation. Structure-function relationship studies have also been performed on retinoidal benzoic acid derivatives in the TOC assay.
