Induction of transforming growth factor alpha in irradiated mouse jejunum

Purpose: To determine the involvement of the mitogenic growth factors trans forming growth factor alpha (TGF alpha), epidermal growth factor (EGF), and the EGF receptor (EGF-R) in the proliferative response after irradiation o f the mouse jejunum. Methods and Materials: C3Hf/Kam mice were whole-body irradiated with 5 and 11 Gy 250 kV X rays. Mice were killed 1-10 days after irradiation, and immu nohistochemistry, in situ hybridization (ISH), and RNase protection assays were performed. Results: Damage to the jejunal crypts caused by irradiation resulted in a s trong proliferative response 1-5 days after 5 Gy and 3-6 days after 11 Gy. Expression of TGF alpha, EGF, and EGF-R increased at 1-2 days and decreased at 4-8 days after 5- or 11-Gy irradiation. Also, TGF alpha mRNA increased during the early phase of the proliferative response (1-2 days after 5 or 1 1 Gy) followed by a decrease at 4 days after 5 Gy and 8 days after 11 Gy. Conclusion: These data indicate that, at the beginning of the proliferative response after irradiation, the transcription of TGF alpha mRNA is increas ed, and that it is inhibited just before compensatory proliferation decreas es. Thus, active regulation of TGF alpha expression takes place at least at the transcriptional level, resulting in upregulation of TGF alpha producti on and increased TGF alpha levels in the crypts during the proliferative re sponse. (C) 1998 Elsevier Science Inc.