ROXY-16-ENE-23-YNE-26,27-HEXAFLUOROCHOLECALCIFEROL (RO24-5531), A NEWDELTANOID (VITAMIN-D ANALOG) FOR PREVENTION OF BREAST-CANCER IN THE RAT

We have used the vitamin D analogue, roxy-16-ene-23-yne-26,27-hexafluo rocholecalciferol (Ro24-5531), for inhibition or mammary carcinogenesi s induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first treated with a single dose of either 15 or 50 mg/kg body w eight NMU and then fed Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly extended tumor latency and lessened t umor incidence as well as tumor number in rats treated with the lower dose of NMU. In rats treated with the higher dose of NMU, Ro24-5531 wa s fed in combination with tamoxifen; in these experiments, Ro24-5531 s ignificantly enhanced the ability of tamoxifen to reduce total tumor b urden, as well as to increase the probability that an animal would be tumor free at the end of the experiment. In vitro, Ro24-5531 was 10-10 0 times more potent than 1,25-dihydroxyvitamin D3, for inhibition of p roliferation of human breast cancer cell lines as well as primary cult ures of cells from 2 patients with acute myelogenous leukemia. When fe d chronically, Ro24-5531 did not elevate serum calcium in the present studies. We propose the new term, ''deltanoids,'' for the set of molec ules composed of vitamin D and its synthetic analogues. in a manner si milar to the naming of ''retinoids'' for the corresponding set of mole cules related to vitamin A.