Induction of transforming growth factor alpha in irradiated mouse jejunum

Purpose: To determine the involvement of the mitogenic growth factors transforming growth factor alpha (TGFα), epidermal growth factor (EGF), and the EGF receptor (EGF-R) in the proliferative response after irradiation of 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 immunohistochemistry, in situ hybridization (ISH), and RNase protection assays were performed. Results: Damage to the jejunal crypts caused by irradiation resulted in a strong proliferative response 1-5 days after 5 Gy and 3-6 days after 11 Gy. Expression of TGFα, EGF, and EGF-R increased at 1-2 days and decreased at 4-8 days after 5- or 11-Gy irradiation. Also, TGFα mRNA increased during the early phase of the proliferative response (1-2 days after 5 or 11 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 TGFα mRNA is increased, and that it is inhibited just before compensatory proliferation decreases. Thus, active regulation of TGFα expression takes place at least at the transcriptional level, resulting in upregulation of TGFα production and increased TGFα levels in the crypts during the proliferative response.