UTL-5g Lowers Levels of TGF-β and TNF-α Elevated by Lung Irradiation and Does Not Affect Tumor-response to Irradiation

UTL-5g is a small-molecule TNF- inhibitor having chemoprotective and liver radioprotective effects. We investigated the effects of UTL-5g on lung irradiated mice and whether UTL-5g affects tumor responses to radiotherapy. C57BL/6 mice were individually treated with UTL-5g at 15, 30, and 60 mg/kg and amifostine (200 mg/kg) by i.p. injection 30 min prior to lung irradiation of 6 Gy (daily x 5). Two mice in the amifostine group died within 8 wks. At the first time point (8 wks), the plasma levels of TGF-β elevated by irradiation were significantly reduced by UTL-5g at 60 mg/kg (p 60 days after lung irradiation). The results indicate that UTL-5g may protect melanocytes against radiation-induced injury. Next, the effects of UTL-5g on tumor response were investigated in CD-1 nu/nu athymic nude mice bearing intramuscular A549 tumors (human non-small cell lung carcinoma) implanted in the right gastrocnemius muscle. Animals were treated with UTL-5g (30 mg/kg i.p.) 30 min prior to or after irradiation (5 Gy) daily for five days. The results showed that UTL-5g did not protect tumor from radiation damage. These observations suggest that UTL-5g may be lung radioprotective and thus, warranted further investigation.