Treatment with 1-alpha,25-dihydroxyvitamin D₃ (vitamin D ₃) to inhibit carcinogenesis in the hamster buccal pouch model

Objective: To investigate whether systemic therapy with 1-alpha,25-dihydroxyvitamin D₃ (vitamin D₃ [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 μg/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 VD₃ 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±6.6mm 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 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.