Abstract PO-058: Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac troponin T in the rat

Abstract

Abstract Radiation-induced heart disease represents a significant health risk 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 models, 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 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 via elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0 Gy treatment revealed inflammation and a 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 10.0 Gy irradiation, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated γ-H2AX. Using proteomic analyses, several novel proteins showed a marked carbonylation profile including those associated with mitochondrial homeostasis and cardiac contractility, most notably, cardiac troponin T. Overall, we present findings of acute oxidative protein, DNA damage, and long-term cardiomyopathy in the irradiated animals, along with oxidative proteomic markers of acute damage. Citation Format: Elliot Rosen. Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac troponin T in the rat [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-058.