Posters— Radiation Oncology

EFFECTS OF IRRADIATION AND RADIO-PROTECTANT ON RAT GROWTH PLATE MORPHOLOGY

Damron TA, Spadaro JA, Farnum CE, Margulies BS, Strauss J (Upstate Medical University Department of Orthopedic Surgery, Syracuse, NY 13224)

Introduction: Previous work in our laboratory has shown a beneficial effect on rat limb growth from administration of the radioprotectant amifostine. The histological correlates of these quantitative measurements of limb length have not previously been described. Purpose: The purpose of this paper is to detail the histological changes over time in the rat growth plate (GP) following irradiation with and without the radioprotectant amifostine.

Methods: Histological specimens were examined from 84 four week-old, Sprague-Dawley male rats previously included in reports detailing limb length effects. Groups of n=6 included for analysis were cage controls at 6 weeks, irradiation only (single dose 12.5 Gy and 17.5 Gy) at 6 weeks, radioprotectant pretreatment (100 mg/kg and 300 mg/kg amifostine for the 12.5 Gy groups and 100 mg/kg for the 17.5 Gy groups) at 6 weeks, and early timing (0.5 week, 1 week, 2 weeks, 3 weeks, and 4 weeks post 17.5 Gy with and without amifostine 100 mg/kg). Irradiation was administered to the right distal femur and proximal tibia; the left leg served as the control.

Results: Morphology of the irradiated GP changed consistently over time. At 0.5 weeks, subtle decrease in cellular profiles with maintenance of overall zonal architecture was evident. At 1 week, cellular profiles were notably reduced, and zonal architecture was nearly lost. At 2 weeks, the GP was composed of sparsely situated terminal, hypertrophic-appearing chondrocytes. At 3 weeks, cellular profiles increased via clonal bodies. At 4 and 6 weeks, clonal bodies predominated. Growth plate cellular profile area following irradiation hit a nadir at 2 weeks and rebounded at the 3rd week toward normal. TRAP staining showed an increase in osteoclasts between the 2 and 3 week time periods that corresponded to an relative decrease in GP height over the same interval. Epifluorescent growth rates reached a nadir 1 week following irradiation and slowly returned toward normal thereafter. Growth plate overall height was greater for controls than irradiated specimens at all time periods, but these effects were much greater centrally than peripherally. Amifostine effects, however, were observed more consistently at the periphery rather than in the central GP.

Discussion: Irradiation results in a predictable pattern of histologic changes, with the greatest effects observed at 1 week in the rat proximal tibia. Prereatment with amifostine is unable to preserve normal GP morphology despite its maintenance of longitudinal growth, but many parameters are statistically improved compared to the irradiated specimens.