Relationship between binding affinities to cellular retinoic acid-binding protein and in vivo and in vitro properties for 18 retinoids.
A new rapid assay has been developed for measurement of the binding of [3H]retinoic acid to cellular retinoic acid-binding protein. The assay, which uses activated charcoal for the separation of bound from unbound retinoic acid, was used to determine the concentration required to inhibit the binding of [3H]retinoic acid to cellular retinoic acid-binding protein by 50% for 18 retinoids with free carboxylic acid groups. Partially purified cellular retinoic acid-binding proteins isolated from rat testes and carcinogen-induced rat mammary tumors were used for these determinations. The following parameters were also determined for some or all of the retinoids: hypervitaminosis A doses; activity against carcinogen-induced mouse skin papillomas; inhibition of growth of a rat chondrosarcoma; inhibition of growth of 3T6 cells; and differentiation of the embryonal carcinoma cell line PCC4.azaIR. While all retinoids that are potent in these biological test systems bind tightly to cellular retinoic acid-binding protein, the converse is not true. The lack of a consistent quantitative correlation between 50% inhibitory concentration and biological activity is probably due to insufficient concentrations of the retinoid in the target tissue or celll, which is a consequence of factors such as absorbability, metabolism, tissue distribution, and pharmacokinetics.
D000818:Animals; D001667:Binding, Competitive; D002813:Chondrosarcoma / Q000517:prevention & control; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000517:prevention & control; D010212:Papilloma / Q000517:prevention & control; D051381:Rats; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000517:prevention & control; D013737:Testis / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D012177:Retinol-Binding Proteins; D014801:Vitamin A; D014212:Tretinoin