Intrinsic radiation resistance in human chondrosarcoma cells
Section snippets
Methods
Cell culture and viral transduction. Three chondrosarcoma cell lines were used in the present study. These were established from a grade II myxoid chondrosarcoma (CS-7), a grade I chondrosarcoma (CS-8), and a grade III chondrosarcoma (CS-9). Three normal chondrocyte cell strains were established from normal (non-osteoarthritic) femoral head cartilage (F), tibial plateau cartilage (TP), and distal femur chondrocytes (DF). All cell cultures were established as described [14]. In brief, cells from
Results
Western blot analyses show that the three chondrosarcoma cell lines used here were p16-deficient but expressed levels of p53, and pRb comparable to the levels found in normal chondrocyte strains (Fig. 1).
Clonogenic survival assays showed a strong, dose-dependent effect of γ-radiation on normal chondrocytes (Fig. 2). Survival in these cells was reduced to an average of 40% at 1 Gy, 21% at 2 Gy, 6% at 3 Gy, and to less than 0.8% at 5 Gy. Chondrosarcoma cell survival was significantly greater than
Discussion
In this study, we found that p16-deficient chondrosarcoma cells were intrinsically more radiation resistant than normal chondrocytes and that restoring p16 activity also restored radiation sensitivity. These results indicated that p16 loss could account for some of the intrinsic radioresistance of these cells. Comet assay data showed that radiation resistant, p16-deficient chondrosarcoma cells sustained levels of radiation-induced DNA damage comparable to the damage seen in p16ink4a-transduced
Uncited reference
[23].
Acknowledgments
This work was supported by the Ben Ling Chondrosarcoma Research Fund and the University of Iowa Department of Orthopaedics and Rehabilitation. The authors are grateful to Terese Nickol, Farshid Moussavi-Harami, and Gail Kurriger for expert technical assistance.
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