Treatment with 1-alpha,25-dihydroxyvitamin D3 (vitamin D3) to inhibit carcinogenesis in the hamster buccal pouch model.

OBJECTIVE To investigate whether systemic therapy with 1-alpha,25-dihydroxyvitamin D(3) (vitamin D(3) [hereinafter, VD(3)]) prevents tumor formation in a hamster buccal pouch model of carcinogenesis. DESIGN Randomized trial in which a known carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was applied to the buccal pouch of 40 hamsters. Animals were randomized to receive systemic VD(3) or no treatment and killed at 2, 6, and 14 weeks after the initiation of DMBA exposure. SETTING Academic medical center. SUBJECTS Forty male golden Syrian hamsters, aged 5 to 6 weeks, were used. INTERVENTIONS A dose of 0.25 mug/kg of VD(3) via intraperitoneal injection was given to 20 animals 3 times per week. Of the remaining 20 control animals, 5 received placebo vehicle injection, and 15 received no further treatment. MAIN OUTCOME MEASURES Timing, size, and number of tumors that developed in the 2 groups. RESULTS Only 1 hamster treated with VD(3) developed a confirmed neoplasm compared with 7 of the control animals (P < .01). The mean +/- SD total diameter of gross lesions per animal in the VD(3)-treated group was 1.2 +/- 1.9 mm compared with 6.8 +/- 6.6 mm in the control group (P = .03). The time to onset of lesion formation was significantly delayed in those animals treated with VD(3), with a mean +/- SD time to development of 13.4 +/- 0.9 weeks, while the control animals developed lesions at 11.2 +/- 1.7 weeks (P = .02). CONCLUSIONS Systemic VD(3) therapy delays carcinogenesis in the hamster buccal pouch model. Further investigation into the mechanisms through which VD(3) inhibits carcinogenesis may lead to development of effective chemopreventive agents to combat head and neck cancer.