Abstract 3940: Acute total body ionizing radiation induces long-term adverse effects and immediate changes in cardiac protein oxidative carbonylation in the rat

Abstract

Abstract Radiation-induced heart disease presents a significant challenge in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the Wistar-Kyoto and spontaneously hypertensive rat model, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body irradiation at two, four, and fifty-two weeks. We further examined irreversible oxidative protein carbonylation in the heart immediately following irradiation. Both males and females sustained reduced growth and anemic conditions over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected by elevated IL-6 serum levels in males at four weeks. Serum cardiac troponin T and I analyses revealed indications of cardiomyopathy at earlier time points while more variability in the troponin levels was observed at one year. Echocardiography at two weeks following 5.0Gy treatment revealed hypertrophy and decrease in cardiac output in the short term, but significant differences were not observed at the one-year timepoint. Cardiac output was decreased in both males and females after two weeks, and statistically significant in females. Following irradiation, the heart tissue showed an increase in total protein carbonylation accompanied by DNA damage indicated by an increase in γ-H2AX. We present novel findings of several proteins that showed a marked change in carbonylation profile including those of mitochondrial origin. Overall, we present findings of acute oxidative protein, DNA damage, and long-term cardiomyopathy in the irradiated animals. Citation Format: Elliot T. Rosen, Dmitry Kryndushkin, Baikuntha Aryal, Yanira Gonzalez, Leena Chehab, Jennifer Dickey, Steven Mog, V Ashutosh Rao. Acute total body ionizing radiation induces long-term adverse effects and immediate changes in cardiac protein oxidative carbonylation in the rat [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3940.