Radiotherapy can potentially inflict serious damage on healthy normal organs. For example, pneumonitis and fibrosis are two well-recognized adverse effects from lung cancer radiotherapy: Currently, amifostine (Ethyol[unreadable]) is the only approved radioprotector indicated to reduce xerostomia associated with radiotherapy of head-and-neck cancer;there is no data supporting the radioprotection by amifostine. Several clinical studies indicated that TNF-&#61537;biologics may be effective in treating radiation pneumonitis. However, biologics are inconvenient to administer, and have been reported to be associated with potentially serious side effects. In this proposal, a small-molecule TNF-&#61537;modulator, UTL-5g, will be investigated for its potential to treat lung injury induced by radiation. The specific aims are: (1) To examine whether tumor cell-killing by irradiation is reduced by UTL-5g in vitro;(2) To show that UTL-5g is effective in reducing lung injury induced by irradiation in a dose-dependent manner in vivo;(3)To show that UTL-5g does not affect tumor cell-killing induced by irradiation in vivo. Successful completion of this study will prove the feasibility of using UTL-5g for treating radiation-induced lung injury. The ultimate goal of this project is to work with or license to a major pharmaceutical company and develop a significantly improved radioprotector for lung radiotherapy.