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, VD3]) 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 VD3 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 mu g/kg of VD3 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, 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 VD3-treated group was 1.2 +/- 1.9 mm compared with 6.8 +/- 6.6 turn in the control group (P =.03). The time to onset of lesion formation was significantly delayed in those animals treated with VD3, with a mean +/- SD time to development of 13.4 +/- 0.9 weeks, while the control animals developed lesions at 11.2 +/- 1.7weeks (P=.02). Conclusions: Systemic VD3 therapy delays carcinogenesis in the hamster buccal pouch model. Further investigation into the mechanisms through which VD3 inhibits carcinogenesis may lead to development of effective chemopreventive agents to combat head and neck cancer.