PARENT SESSION

Experimental and Clinical Therapeutics

(PP201) Development of biomarkers in radiation-induced lung damages.

Song, Jie-Young ¹, Lim, Hee-Soon ¹, Kim, Hyung-Doo , Han, Youngsoo¹, Son, Hyeog-Jin ¹, Yun, Yeon-Sook¹, ¹ Laboratory of Radiation Immunology, nowon-ku, Seoul, Republic of Korea

ABSTRACT- The accurate system to predict the response to radiotherapy for individual cancer lesions is highly demanded for increasing therapeutic accomplishment. The aim of this study was to find some possible markers that can provide a tinge clue to predict adverse effect of radiotherapy. In order to generate radiation-induced lung injured model, C57BL/6 (radiosensitive) mice were exposed to local whole-thorax irradiation using ⁶⁰Co -rays from a Theratron 780 irradiation unit (15 Gy, dose rate 0.76 Gy/min). Several times after irradiation (1 day, 2, 16, 26 weeks), we investigated changes in the expression of some molecules, which included cytokines (IFN-, IL-5), fibrosis related growth factors (TGF-s, TIMPs) and antioxidant enzymes (Mn-SOD, HO-1) by semi-quantitative RT-PCR. In addition, H/E staining for pathological diagnosis and hydroxyproline assay as a marker of fibrosis were coincidently accompanied to the irradiated lung. One day after irradiation, the expression level of IFN- was significantly increased but IL-5 was decreased, and slowly went back to the normal level after 2 wks. Interestingly, the mRNA of IFN- was highly increased at 26 wks after irradiation, suggesting the presence of the second wave for the upregulation of IFN- gene in addition to the first wave in early period after irradiation. TGF-₁ and Mn-SOD expressions were increased 1 day after irradiation, but was not shown some alterations after that. HO-1 mRNA was continuously increased until 16 wks after irradiation, however TIMP1 was substantially increased from that point. We also detected some histological changes such as collection of alveolar macrophages, moderate patch of inflammatory cell infiltration, local alveolar destruction, and mild lay-down of collagens supported by hydroxyproline assay. Based on the above results, we suggest that the role of IFN- in early time and TIMP1 in late time might be possible molecular markers to detect lung damages induced by irradiation.

Key words: radiation, lung, IFN-gamma, TIMP