Toxicity and dose-response studies of 1α-hydroxyvitamin D2 in a retinoblastoma xenograft model

Richard J. Grostern, Paul J. Bryar, Michele L. Zimbric, Soesiawati R. Darjatmoko, Boaz J. Lissauer, Mary J. Lindstrom, Janice M. Lokken, Stephen A. Strugnell, Daniel M. Albert

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background: Although calcitriol (1,25-dihydroxycholecalciferol) and vitamin D2 inhibit retinoblastoma growth in the athymic (nude) mouse xenograft (Y-79 cell line) model of retinoblastoma, they can cause severe toxicity. Objective: To examine the toxicity of and dose-dependent response for the inhibition of tumor growth for 1α-hydroxyvitamin D2 (1α-OH-D2), an analogue with reduced systemic toxicity, in the athymic Y-79 mouse model. Methods: Mice were randomized into treatment and control groups for 5-week toxicity and dose-response studies. Treatment was via oral gavage 5 times per week. Dose-response studies measured tumor inhibition and drug serum levels. Tumor size and body weight were measured weekly together with various criteria for toxicity. Animals were euthanized at the end of the treatment period. Tumors and kidneys were harvested, and serum was analyzed for calcium and drug levels. Results: Doses of 0.1 to 1.2 μg/d were selected on the basis of toxicity studies for the dose-response trial. Tumor weight and volume in the 0.2-μg and 0.3-μg doses were significantly lower than in controls. Mortality rates and kidney calcification in mice treated with doses of 0.1 to 0.3 μg were lower than those observed in studies of calcitriol and vitamin D2. Conclusion: A vitamin D analogue, 1α-OH-D2, inhibits tumor growth in this xenograft model of retinoblastoma with less toxicity than calcitriol and vitamin D2.

Original languageEnglish (US)
Pages (from-to)607-612
Number of pages6
JournalArchives of ophthalmology
Volume120
Issue number5
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Ophthalmology

Fingerprint Dive into the research topics of 'Toxicity and dose-response studies of 1α-hydroxyvitamin D<sub>2</sub> in a retinoblastoma xenograft model'. Together they form a unique fingerprint.

  • Cite this

    Grostern, R. J., Bryar, P. J., Zimbric, M. L., Darjatmoko, S. R., Lissauer, B. J., Lindstrom, M. J., Lokken, J. M., Strugnell, S. A., & Albert, D. M. (2002). Toxicity and dose-response studies of 1α-hydroxyvitamin D2 in a retinoblastoma xenograft model. Archives of ophthalmology, 120(5), 607-612. https://doi.org/10.1001/archopht.120.5.607