Induction of transforming growth factor alpha in irradiated mouse jejunum.
OBJECTIVE
To determine the involvement of the mitogenic growth factors transforming growth factor alpha (TGF alpha), epidermal growth factor (EGF), and the EGF receptor (EGF-R) in the proliferative response after irradiation of the mouse jejunum.


METHODS
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 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 11 Gy) followed by a decrease at 4 days after 5 Gy and 8 days after 11 Gy.


CONCLUSIONS
These data indicate that, at the beginning of the proliferative response after irradiation, the transcription of TGF alpha mRNA is increased, and that it is inhibited just before compensatory proliferation decreases. Thus, active regulation of TGF alpha expression takes place at least at the transcriptional level, resulting in upregulation of TGF alpha production and increased TGF alpha levels in the crypts during the proliferative response.
Ruifrok
A C
AC
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Weil
M M
MM
Mason
K A
KA
Thames
H D
HD
D000818:Animals; D002452:Cell Count / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007583:Jejunum / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008871:Microvilli / Q000378:metabolism / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D011829:Radiation Dosage; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors