Toxicity and dose-response studies of 1,25-(OH)2-16-ene-23-yne vitamin D3 in transgenic mice

Craig L. Wilkerson, Soesiawati R. Darjatmoko, Mary J. Lindstrom, Daniel M. Albert

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The vitamin D3 analogue 1,25-(OH)2-16-ene-23-yne vitamin D3 (16,23- D3) in doses with low systemic toxicity has been demonstrated to inhibit retinoblastoma growth in transgenic mice. This study examines the dose- dependent response for inhibition of tumor growth in transgenic mice with retinoblastoma and evaluates the in vivo toxicity of 16,23-D3 in nontransgenic mice. Transgenic 8-10-week-old mice with retinoblastoma (n = 119) were randomly assigned to groups receiving 1.0, 0.75, 0.5, 0.35, 0.2, or 0.05 μg of 16,23-D3 and a vehicle alone (control) group i.p. five times a week for 5 weeks. An additional control group received no injection. Eyes were enucleated one week after the end of treatment, and tumor areas were measured. To determine the toxic dose, transgene-negative littermates received 0.5, 1.0, 1.5, 2.5, 3.5, 4.5, or 5.0 μg of 16,23-D3, and control groups received vehicle alone, 5 days a week for 5 weeks. Serum calcium levels were measured, and necropsies were performed on animals from each group. In the dose-response study, tumor growth inhibition was greatest in the group receiving 0.35 μg (55% inhibition; P = 0.0056) and was also significant in the group receiving 0.5 μg (42% inhibition; P = 0.036). The systemic toxic effects due to hypercalcemia occurred at doses of ≤1.0 μg. 16,23-D3 inhibits tumor growth at doses ≤0.35 μg and shows toxic effects at doses ≤1.0 μg related to hypercalcemia in mice fed an unrestricted diet. No toxicity was observed with lower doses.

Original languageEnglish (US)
Pages (from-to)2253-2256
Number of pages4
JournalClinical Cancer Research
Volume4
Issue number9
StatePublished - Sep 1 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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