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Journal of Bone and Mineral Metabolism

, Volume 12, Supplement 1, pp S165–S168 | Cite as

Effects of gallium nitrate in nude mice bearing a canine adenocarcinoma model of humoral hypercalcemia of malignancy: Biochemical, histomorphometric, and ultrastructural investigations

  • Charles C. Capen
  • Hiroyuki Okada
  • Joyce I. Merryman
  • Thomas J. Rosol
Article

Abstract

Hypercalcemic nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy (HHM) were treated daily with gallium nitrate (60 mg/kg elemental gallium subcutaneously on day 0 followed by 20 mg/kg day for four days. Concentrations of gallium in bone were undetectable (<0.00005 µg/g bone) in vehicle-treated mice but markedly elevated in gallium-treated mice (>235 ± 6 µg/g bone). Gallium nitrate significantly decreased serum calcium and urinary calcium excretion in tumor-bearing mice compared with vehicle-treated controls. Histomorphometric evaluation of lumbar vertebrae revealed a significant decrease in the number of osteoclasts/mm trabecular bone in gallium-treated tumor-bearing mice compared with controls. Osteoclasts from tumor-bearing mice treated with gallium nitrate were significantly decreased in size, had reduced tartrate-resistant acid phosphatase staining intensity and ultrastructurally had fewer intracytoplasmic vesicles compared with vehicle-treated controls. Osteoclasts in gallium-treated mice were small and flattened with poorly developed cytoplasmic organelles. The findings of this investigation indicated that gallium nitrate reduced serum calcium in an animal model of HHM by inhibiting osteoclastic bone resorption.

Key Words

gallium nitrate humoral hypercalcemia of malignancy nude mouse parathyroid hormone-related protein bone histomorphometry ultrastructure osteoclasts osteoblasts 

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Copyright information

© Japanese Society of Bone Metabolism Research 1994

Authors and Affiliations

  • Charles C. Capen
    • 2
  • Hiroyuki Okada
    • 1
  • Joyce I. Merryman
    • 2
  • Thomas J. Rosol
    • 2
  1. 1.Rakuno Gakuen UniversityHokkaidoJapan
  2. 2.Department of Veterinary PathobiologyThe Ohio State UniversityColumbusUSA

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