1 alpha-hydroxyvitamin D3, hypercalcemia, and growth suppression of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors

Abstract

1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] was administered to female Sprague-Dawley rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. 1 alpha(OH)D3 suppressed the growth of the rat mammary tumors dose-dependently, and in the high dose groups treated with 0.5-1.0 micrograms/kg of 1 alpha(OH)D3, significant inhibition of tumor growth was observed. But daily oral administration of 1 alpha(OH)D3 for four consecutive weeks caused side effects such as hypercalcemia and weight loss. We compared 0.5 microgram/kg of 1 alpha(OH)D3 three times weekly with the same dose six times weekly to discover whether or not the side effects can be reduced by treatment schedule. Both groups showed a significant oncostatic effect, compared with the control group, while the side effects were relieved in the three times weekly group. Regarding estrogen receptors (ER) in the tumors, there was no significant difference among the groups. These results suggested that the antitumor effect of 1 alpha(OH)D3 on DMBA-induced mammary tumors was not related to ER status. Combined use of 1 alpha(OH)D3 with 5-fluorouracil (5-FU) or medroxyprogesterone acetate (MPA) was also examined. No significant augmentation of the antitumor effect was seen in the two combinations, although the combined therapy with MPA showed a significant inhibition of weight loss in the rats.