Abstract 5465: Persistent oxidative stress in mouse intestinal and colonic epithelial cells after exposure to 12C-ion radiation

Abstract

Abstract Purpose: 12C-ion radiotherapy is demonstrating favorable results compared to photon radiotherapy for select cancers. While normal tissue exposure is lower with 12C-ions relative to γ-rays, it cannot be completely eliminated and therefore, late tissue toxicity, inflammation and secondary carcinogenesis cannot be ruled out. The goal of this study was to assess the extent of persistent oxidative stress (POS) after 12C radiation exposure and compare the results to that after γ radiation exposure. Methods and Materials: Mice (C57BL/6J; 6 to 8 weeks; male) were irradiated with 0.5 or 1.3 Gy of γ or 12C-ion, and intestinal (IEC), colonic (CEC) epithelial cells and tissues were collected 2 months after radiation exposure. In epithelial cells, intracellular ROS, mitochondrial superoxide, mitochondrial membrane potential (MMP), and cardiolipin oxidation were studied by flow-cytometry. Superoxide dismutase (SOD), catalase, and NADPH oxidase activity along with lipid oxidation were also assessed in epithelial cells using biochemical assays. Results: Our results clearly showed radiation quality and dose-dependent induction of POS. Both intestine and colon showed a higher elevation of intracellular ROS, mitochondrial superoxide, NADPH oxidase activity, and mitochondrial cardiolipin oxidation after 12C relative to γ radiation. Moreover, antioxidant enzyme activity in intestine and colon was also significantly reduced in 12C-irradiated mice. Compared to γ radiation, membrane lipid damage was remarkably higher in both intestine and colon of 12C-ion irradiated mice. At 0.5 Gy, persistent oxidative damage indicated by 4-hydroxynonenal was 3-fold in colon and 1.6 fold in intestine after 12C relative γ radiation. Conclusions: Mitochondrial deregulation, increased NADPH oxidase activity and loss of SOD and catalase activities were the major contributory events in 12C-ion-induced POS in mouse GI-tissues. Compared to intestine, colon was more susceptible to POS induction that might be due to progressive cell turnover in intestine resulting in faster elimination of initial damage signal in a given time than colon. Taken together, our data suggest that normal tissue exposure to 12C radiation carries higher long-term risk relative to γ-rays at comparable doses and further detail evaluation is warranted. Citation Format: Shubhankar Suman, Santosh Kumar, Albert J. Fornace, Kamal Datta. Persistent oxidative stress in mouse intestinal and colonic epithelial cells after exposure to 12C-ion radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5465. doi:10.1158/1538-7445.AM2017-5465