Retinoid toxicity for fibroblasts and epithelial cells is separable from growth promoting activity

Three different retinoids with widely varying capacity to stimulate skin repair in vivo and stimulate fibroblast and epithelial cell growth in vitro were examined for capacity to lyse the same cells at high concentrations. These included all-trans retinoic acid (RA), tetrahydro tetramethyl napthalenyl benzoic acid (TTNPB), and its biologically inactive structural analogue, meta-carboxy TTNPB. Despite their differing capacities to stimulate skin repair and cell growth, all of the agents were cytotoxic for fibroblasts and epithelial cells over the same range of concentrations (0.6-3 x 10(-5) M). Cytotoxicity for both fibroblasts and epithelial cells was blocked by addition of phosphatidylcholine to the cells along with the retinoid. In the presence of high concentrations of RA (0.75-3 x 10(-5) M) and phosphatidylcholine, proliferation was observed. The proliferative response was greater under these conditions than in the presence of an optimal concentration of RA (0.75-3 x 10(-6) M) without phosphatidylcholine. These data suggest that toxicity of retinoids can be separated, at least partially, from their growth-promoting activities.