Development of an intramuscular xenograft model of canine osteosarcoma in mice for evaluation of the effects of radiation therapy.

Abstract

OBJECTIVE: To develop an IM xenograft model of canine osteosarcoma in mice for the purpose of evaluating effects of radiation therapy on tumors. ANIMALS: 27 athymic nude mice. PROCEDURES: Mice were randomly assigned to 1 of 3 groups of 9 mice each: no treatment (control group), radiation at 10 Gy, or radiation at 15 Gy. Each mouse received 5 x 10(5) highly metastasizing parent osteosarcoma cells injected into the left gastrocnemius muscle. Maximum tumor diameter was determined with a metric circles template to generate a tumor growth curve. Conscious mice were restrained in customized plastic jigs allowing local tumor irradiation. The behavior and development of the tumor xenograft were assessed via evaluations of the interval required for tumor-bearing limbs to reach diameters of 8 and 13 mm, extent of tumor vasculature, histomorphology of tumors, degree of tumor necrosis, and existence of pulmonary metastasis and clinical disease in affected mice. RESULTS: Tumor-bearing limbs grew to a diameter of 8 mm (0.2-g tumor mass) in a mean +/- SEM interval of 7.0 +/- 0.2 days in all mice. Interval to grow from 8 to 13 mm was significantly prolonged for both radiation therapy groups, compared with that of the control group. Histologic evaluation revealed the induced tumors were highly vascular and had characteristics consistent with those of osteosarcoma. Pulmonary metastasis was not detected, and there was no significant difference in percentage of tumor necrosis between groups. CONCLUSIONS AND CLINICAL RELEVANCE: A reliable, repeatable, and easily produced IM xenograft model was developed for in vivo assessment of canine osteosarcoma.