Intrinsic radiosensitivity and repair of sublethal radiation-induced damage in canine osteosarcoma cell lines

Am J Vet Res. 2008 Sep;69(9):1197-202. doi: 10.2460/ajvr.69.9.1197.

Abstract

Objective: To characterize the radiosensitivity and capacity for sublethal damage repair (SLDR) of radiation-induced injury in 4 canine osteosarcoma cell lines.

Sample population: 4 canine osteosarcoma cell lines (HMPOS, POS, COS 31, and D17).

Procedures: A clonogenic colony-forming assay was used to evaluate the cell lines' intrinsic radiosensitivities and SLDR capacities. Dose-response curves for the cell lines were generated by fitting the surviving fractions after radiation doses of 0 (control cells), 1, 2, 3, 6, and 9 Gy to a linear quadratic model. To evaluate SLDR, cell lines were exposed to 2 doses of 3 Gy (split-dose experiments) at an interval of 0 (single 6-Gy dose), 2, 4, 6, or 24 hours, after which the surviving fractions were assessed.

Results: Mean surviving fraction did not differ significantly among the 4 cell lines at the radiation doses tested. Mean surviving fraction at 2 Gy was high (0.62), and the alpha/beta ratios (predictor of tissue sensitivity to radiation therapy) for the cell lines were low (mean ratio, 3.47). The split-dose experiments revealed a 2.8- to 3.9-fold increase in cell survival when the radiation doses were applied at an interval of 24 hours, compared with cell survival after radiation doses were applied consecutively (0-hour interval).

Conclusions and clinical relevance: Results indicated that these canine osteosarcoma cell lines are fairly radioresistant; alpha/beta ratios were similar to those of nonneoplastic, late-responding tissues. Future clinical investigations should involve increasing the fraction size in a manner that maximizes tumor killing without adverse effects on the nonneoplastic surrounding tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / pathology
  • Bone Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Dog Diseases / radiotherapy*
  • Dogs
  • Dose-Response Relationship, Radiation
  • Osteosarcoma / pathology
  • Osteosarcoma / radiotherapy*
  • Radiation Tolerance*
  • Time Factors