2002 CTOS Annual Meeting Posters — Radiation Oncology

IMMUNOHISTOCHEMICAL BASIS FOR COMBINATION RADIOPROTECTANT TREATMENT WITH AMIFOSTINE AND PENTOXIFYLLINE FOR GROWTH PLATE PROTECTION DURING IRRADIATION
[Abstract ID: 28]

Category: Radiation Oncology

Authors: Timothy A. Damron¹, Sharad Mathur¹, Judy Strauss¹, Lee Reichel¹, Bryan Margulies¹, Yi Yang¹, Steve Landas¹, Cornelia Farnum², William Grant¹, Joseph A. Spadaro¹

Author Institutions: ¹SUNY Upstate Medical University at Syracuse, New York, United States; ²Cornell University College of Veterinary Medicine, New York, United States

Presenter: Timothy A. Damron
tdamron@twcny.rr.com

Correspondent: Timothy A. Damron
tdamron@twcny.rr.com
Syracuse New York United States 13202
Ph: 315-464-4472
Fax: 315-464-4664

Objectives: Irradiation of the growth plate during treatment of extremity sarcomas in pediatric patients often leads to undesirable late sequelae. Growth plate PTHrP has been reported to be downregulated following irradiation. The purpose of this project was to test the hypotheses that PTHrP rebounds as part of the normal response following growth plate irradiation and that a proven radioprotectant may act to enhance this PTHrP response.

Methods: Sixty weanling 5 week Sprague-Dawley rats underwent right knee irradiation with single fraction 17.5 Gy while the left leg served as internal control. Twelve animals (half pretreated with amifostine) were euthanized at each of 0.5, 1, 2, 3, and 4 weeks. Immunohistochemical staining was performed and analyzed on tissue specimens for 3 animals per group per time for PTHrP, Bcl-2, Bax, caspase, TGF-beta and FGF-2.

Results: Irradiated tissue demonstrated reduced staining for PTHrP early, but by 2 weeks after irradiation there was a notable return in PTHrP expression to at least control levels. This post-irradiation PTHrP response was blunted rather than enhanced by amifostine. Amifostine showed its most dramatic effects in reducing Bax expression. Amifostine did not increase proliferative cytokines.

Conclusions: The observed PTHrP response corresponds to improving growth plate morphology and growth rate, suggesting a role for PTHrP in response to growth plate irradiation. Amifostine appears to decrease apoptosis mediators. This suggests a potential role for complementary radioprotectants that increase or maintain the post-irradiation PTHrP levels, such as pentoxifylline, as a means of maximizing growth plate recovery following irradiation.