Systemic inhibition of tumor promoter-induced ornithine decarboxylase in 1 alpha-hydroxyvitamin D3-treated animals.
Topical application of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], an active form of vitamin D3, was previously shown to inhibit the induction of ornithine decarboxylase (ODC) and tumor promotion by tumor promoters in mouse skin. In the present study, this observation in skin was extended to other tissues, such as the stomach, colon, and liver, using 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3], which is converted to 1 alpha,25(OH)2D3 in the liver without hormonal control and thus evokes the systemic effects, if any, of 1 alpha,25(OH)2D3. When mice were given 1 alpha (OH)D3 at a dose of 5 micrograms by gastric tube, their plasma level of 1 alpha,25(OH)2D3 increased to a peak of about 18-fold the normal level after 12 h, followed by hypercalcemia (about 14 mg/dl), which reached a peak on Days 2 to 3. In 1 alpha (OH)D3-treated mice, induction of epidermal ODC by 12-O-tetradecanoylphorbol-13-acetate was markedly inhibited, the inhibition being maximal 2 to 4 days after 1 alpha (OH)D3 administration. ODC induction in the glandular stomach mucosa of rats by NaCl, a tumor promoter in stomach carcinogenesis, was also inhibited dose and time dependently by 1 alpha (OH)D3. Similarly, 1 alpha (OH)D3 treatment of rats markedly inhibited the induction of ODC in the colon mucosa by deoxycholate, a tumor promoter of colon carcinogenesis, and of ODC in the liver by phenobarbital, a promoter of liver carcinogenesis. These results suggest that an active form of vitamin D3 has a systemic inhibitory effect on induction of ODC activity by tumor promoters.
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003106:Colon / Q000201:enzymology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000201:enzymology; D012965:Sodium Chloride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D006887:Hydroxycholecalciferols; D003840:Deoxycholic Acid; D012965:Sodium Chloride; D009955:Ornithine Decarboxylase; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C008088:alfacalcidol