Association of transforming growth factor beta (TGF-beta) immunoreactivity with specific histopathologic lesions in subacute and chronic experimental radiation enteropathy.
Irradiated intestine consistently exhibits increased immunoreactivity of transforming growth factor beta-1 (TGF-beta 1). It is not known whether this increase occurs secondary to mucosal barrier disruption (consequential injury) or to injury in late-responding tissue compartments (primary radiation enteropathy). This study therefore assessed the association between TGF-beta immunoreactivity and specific consequential and primary histopathologic alterations. A small bowel loop was fixed inside the scrotum in male rats and subsequently exposed to either 18 daily fractions of 2.8 Gy or nine daily fractions of 5.6 Gy orthovoltage X-radiation. Radiation-induced induced intestinal complications were recorded and groups of animals were euthanized 2 and 26 weeks post-irradiation. Radiation injury was assessed with a histopathologic radiation injury score (RIS). Total TGF-beta was detected immunohistochemically and measured with interactive computerized image analysis. The image analysis technique yielded highly reproducible quantitation data. The 2.8-Gy group maintained mucosal integrity and had fewer intestinal complications, lower RIS and lower TGF-beta levels than the 5.6-Gy group. There was highly significant correlation between TGF-beta immunoreactivity and radiation injury at both observation times (P < 0.001 and P < 0.0001). At 2 weeks, TGF-beta immunoreactivity correlated with mucosal ulceration (P = 0.002), epithelial atypia (P = 0.005), and serosal thickening (P = 0.0004). At 26 weeks, TGF-beta levels correlated significantly with six of seven histopathologic parameters, most strikingly with vascular sclerosis (P = 0.0003). We conclude that mucosal barrier breakdown is closely associated with increased TGF-beta immunoreactivity in consequential radiation enteropathy. The highly significant correlation between TGF-beta expression levels and alterations in late-responding tissue compartments also suggest a role for TGF-beta in primary radiation enteropathy.
Richter
K K
KK
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock AR 72205, USA.
Langberg
C W
CW
Sung
C C
CC
Hauer-Jensen
M
M
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004751:Enteritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta