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Acute Effects of Pulsed Low Dose Rate and Conventional Radiotherapies On Normal Mouse Tissues

D Cvetkovic

D Cvetkovic*, B Wang , L Chen , C Ma , Fox Chase Cancer Center, Philadelphia, PA


SU-E-FS1-1 (Sunday, July 30, 2017) 1:00 PM - 1:55 PM Room: Four Seasons 1

Purpose: In our previous subacute and chronic in vivo experiments PLDR radiotherapy reduced the damage to normal mouse tissues relative to CRT for the same dose and regimen; in this study we report on their acute effects.

Methods: Twenty eight male BALB/c nude mice were randomly assigned into a non-irradiated control group (n=4), a CRT group (n=12), and a PLDR group (n=12). Animals received 8Gy total body irradiation (TBI) either continuously at a dose rate of 300MU/min (CRT) or in 0.2Gyx40 pulses separated by 3min intervals (PLDR). Body weights were checked daily and 50% of the mice were sacrificed 24h, the remainder 72h after treatment. Various organs were removed, formalin-fixed, paraffin-embedded and stained with H&E. Morphological changes in mouse tissues were observed under a microscope. Peripheral blood cell counts were determined using VetScan VS2 analyzer.

Results: Histopathological analyses revealed abnormalities in the spleen, bone marrow and small intestine of all treated animals. These were more prominent 72h than 24h after irradiation, irrespective of the treatment modality. There was no significant difference in the level of spleen and small intestine acute toxicity between the PLDR and CRT groups; however the bone marrow atrophy was more severe in the CRT group on day 3. Morphological findings in the bone marrow corresponded to the peripheral white blood cell (WBC) counts, namely WBC count in the CRT group decreased from 38.8% at 24h to 12.3% at 72h vs. 46.6% at 24h to 25.8% at 72h in the PLDR group, relative to control.

Conclusion: In our acute experiment PLDR radiotherapy reduced toxicity in the bone marrow and the peripheral blood after 8Gy TBI in nude mice. Since PLDR produces similar tumor control as CRT, it can be used for treatment of recurrent cancers.

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