Abstract 2505: Exposure to a therapeutically relevant dose of ionizing radiation reveals colorectal cancer biomarker and associated receptor alterations

Abstract

Abstract Purpose: Diagnostic and therapeutic radiation exposure to humans is inevitable, and radiation exposure is known to enhance risks of colorectal cancer (CRC) and inflammatory bowel diseases. Radiation exposure has also been observed to promote obesity in humans as well as in rodents. While altered levels of insulin like growth factor 1 (IGF1), leptin, and adiponectin have been reported as potential markers of obesity-related CRC risk, there is a paucity of long-term radiation-risk-markers for intestinal pathologies. The goal of the current study was to evaluate in mice whether obesity-related CRC risk markers have the potential to serve as radiation-associated CRC risk markers after exposure to a clinically relevant γ radiation dose. Methods and materials: Mice (C57BL/6J, 6-8 week old, female; n= 8 per group) were exposed to a γ radiation dose of 2 Gy, commonly used in fractionated radiotherapy. Serum and intestinal tissues were collected two and twelve months after radiation. Serum levels of IGF-1, IGF binding protein 3 (IGFBP3), leptin, and adiponectin were analyzed by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was performed on small intestine and colon sections for IGF1 receptor (IGF1R), obesity receptor (OB-R), adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2) and proliferative marker Ki-67. Results: The levels of free IGF1 and free leptin measured by calculating IGF1/IGFBP3 and leptin/adiponectin ratio showed a distinct pattern. While significantly higher free IGF1 was observed twelve months post-radiation, higher free leptin was observed two months after radiation exposure. Immunohistochemical analysis demonstrated increased IGF1R and OB-R, decreased AdipoR1 and R2, and increased Ki67 in intestinal as well as in colonic sections at both the time points. Conclusions: Considering that one fraction of 2 Gy showed significant alterations in risk markers, we believe exposure to a higher total dose using more fractions will show more pronounced effects. Taken together, this study demonstrates that adipogenic risk markers of CRC could be effective tools to assess CRC risks after therapeutic γ radiation exposures. Note: This abstract was not presented at the meeting. Citation Format: Shubhankar Suman, Albert J. Fornace, Kamal Datta. Exposure to a therapeutically relevant dose of ionizing radiation reveals colorectal cancer biomarker and associated receptor alterations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2505. doi:10.1158/1538-7445.AM2014-2505