ABSTRACT
Retinoids inhibit the induction of ornithine decarboxylase (ODC) in mouse epidermis and the extent of this inhibition correlates with the ability of retinoids to prevent or inhibit the formation of epidermal tumors caused by tumor promoters. The in vivo ODC and tumor promotion assays are excellent models for assessing retinoid structure-activity relationships as a means of discovering the structural modifications that can be made in the retinoid skeleton that enhance chemopreventive activity. Putrescine is the precursor for the biosynthesis of the polyamines spermine and spermidine, which are essential components for ribosome structure and function. In the ODC assay the retinoids were administered topically, whereas in the papilloma regression assay they were given systemically by intraperitoneal (i.p.) injection. Structural modifications were made in the ring, polyolefinic chain, and polar terminus regions of the retinoid skeleton. Generally, these modifications were systematic in nature to provide data for future quantitative structure-activity correlations.
