Effectiveness of 1–hydroxyvitamin D2 (1–OH–D2) in Inhibiting Tumor Growth in the Tyr–Tag Transgenic Pigmented Ocular Tumor Model

Abstract

Abstract: : Purpose: To study the effectiveness of the vitamin D analog 1α–hydroxyvitamin D₂ (1α–OH–D₂) in inhibiting ocular tumor growth in Tyr–Tag transgenic mice. These animals develop pigmented intraocular tumors primarily from the retinal pigment epithelium which closely resemble the histology and growth pattern of human choroidal melanoma. Methods: A total of 73 Tyr–Tag transgenic mice between six and seven weeks old were randomly assigned by sex and litter to three treatment groups receiving 0.05 µg, 0.1 µg, or 0.2 µg per day of 1α–OH–D₂ and a control group receiving vehicle. The drug was administered by oral gavage five times a week for five weeks. The animals were then euthanized and their eyes were enucleated and processed histologically. Three serial sections from each eye were examined microscopically and the mean tumor area measured using Optimas software version 6.5 (Media cybernetics, LP, Silver Spring, MD). Toxicity was assessed on the basis of mortality, weight loss, serum calcium levels, and kidney calcification. Results: The mean tumor size in the 0.1 and 0.2 µg per day treatment groups was smaller than in the controls (p < 0.001). No significant difference was seen between the 0.05 µg per day treatment group and the controls (p = 0.63). Survival in the 0.1 and 0.2 µg treated groups was lower than the controls (95% versus 85.7% versus 74.7%; p < 0.01). Conclusions: In the Tyr–Tag mouse 1α–OH–D₂ inhibits pigmented ocular tumor growth at moderate drug levels with relatively low mortality.

Keywords: melanoma • tumors • transgenics/knock–outs