Effects of X-ray irradiation on the redox status of mouse colorectal tissues

Abstract

The effects of X-ray irradiation on the redox status of colorectal tissues were investigated using magnetic resonance redox imaging.The pyrrolidine-ring nitroxyl contrast agent, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), was used as a suitable redox-sensitive contrast agent for colorectal tissues. The lower abdomen of an 8-week-old female C3H/HeSlc mouse was X-ray irradiated with a single 10-Gy dose under anesthesia. X-rays were collimated through a 19-mm slit made by a pair of 5-cm-thick lead blocks. MRI experiments using CmP as the contrast agent were conducted on mice irradiated by X-rays at different times, i.e., 2‒8 h, 1, 2, 4, 8, 12, and 16 day(s) after irradiation. Dynamic datasets of multi-slice T1-weighted images were obtained by repeating scans every 20 s for 22 min. The time course of the CmP-induced T1-weighted signal in colorectal tissues was analyzed. The relationship between mitochondrial damage and redox responses was also investigated.The k1 decay rate of CmP, which mainly reflects the biological reduction of nitroxyl radicals in tissue, was significantly suppressed on day 2, increased on day 8, and then recovered to the control level. The decrease in the k1 value on day 2 indicated the inhibition of biological activity in injured tissue. Further animal studies are required to verify the relationship between the redox response of the colorectum tissue and the mitochondrial damages. This magnetic resonance redox imaging technique has the potential to visualize radio-biological responses in the tissues of living animals.

Keywords

• Ionizing radiation
• Radio-biological response
• Tissue redox response
• Magnetic resonance redox imaging
• Nitroxyl radical
• Redox-sensitive contrast agent