IN-VIVO USE OF N-(4-HYDROXYPHENYL RETINAMIDE)-O-GLUCURONIDE AS A BREAST-CANCER CHEMOPREVENTIVE AGENT

The inhibitory effects of N - (4 - hydroxyphenyl) retinamide and its g lucuronide derivative on the development and growth of 7,12 - dimethyl benz (a) anthracene - induced rat mammary tumors in vivo were compared . The results indicate that the glucuronide had a greater chemoprevent ive potency than equimolar concentration of the free retinoid by all t he criteria measured, mainly the inhibition of tumor incidence, multip licity and tumor growth. HPLC analysis of the blood of the rats showed no hydrolysis of the glucuronide during its chronic consumption, indi cating that the retinoid glucuronide is probably acting in vivo per se rather than through hydrolysis to the free retinoid. The higher poten cy and lower toxicity of the glucuronide suggests, for the first time, that the conjugate may have an in vivo chemopreventive advantage over the parent retinamide.