CHEMOTHERAPEUTIC EVALUATION OF N-(4-HYDROXYPHENYL) RETINAMIDE-O-GLUCURONIDE IN THE RAT MAMMARY-TUMOR MODEL

The growth inhibitory effects of N-(4-Hydroxyphenyl) retinamide (II-E- LPR) and its glucuronide derivative, N-(4-Hydroxyphenyl) retinamide-O- glucuronide (4-HPROG) on established DMBA induced rat mammary tumors w ere compared. The results indicate that the glucuronide analog had a g reater antitumor potency than equimolar concentration of the free reti noid Tumor regression occurred in 75% of the rats fed 2 mmol/Kg diet o f 4-HPROG. In a 6-week study, the maximum tolerated dietary dose (MTD) was found to be 3.5 mmol/Kg diet for 4-HPR and 5 mmol/Kg diet in the case of 4-HPROG. The higher potency and lower toxicity of the glucuron ide suggests that this conjugate may have an in vivo chemotherapeutic advantage over the parent free retinoid.