Abstract
Radiotherapy is an important conventional therapeutic modality in the treatment of the malignant thoracic diseases, such as lung cancer. However, the radiation-induced injury to the normal lung tissue, including radiation pneumonitis and lung fibrosis, is sometimes severe and even lethal, and thus, becomes the main dose limiting factor. TGF-|[beta]| and its receptor are known to play a pivotal role for the radiation induced lung damage. In this study, we confirmed that following thoracic irradiation with a single dose of 9 Gy, radiation-induced TGF-|[beta]|1 concentration elevated in serum with biphasic pattern. Therefore, we constructed a replication-defective recombinant adenovirus carrying the soluble TGF-|[beta]| type II receptor cDNA (AdsTGF|[beta]|Rc), which can infect the cells and produce the soluble form of TGF-|[beta]| type II receptor. This soluble receptor can bind TGF-|[beta]| in a dominant-negative form, and consequently block the TGF-|[beta]| function. In vivo experiment, i.p. injection of the AdsTGF|[beta]|Rc in mice before irradiation could suppress the TGF-|[beta]|1 serum elevation and reduced the pneumonitis histologically.
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