Combination of pre-operative radiotherapy and surgery suppresses local accumulation of collagen and TGF-beta1 in rats.
BACKGROUND
The systemic and local tissue repair responses of radiation in combination with surgery are still unclear. We have studied the effect of fractionated pre-operative radiotherapy with or without subsequent laparotomy on collagen accumulation using a rodent model.


METHODS
Thirty-two male Sprague-Dawley rats were divided into four groups (eight rats per group): 1) sham radiation and sham laparotomy (control); 2) sham radiation and laparotomy; 3) radiation and sham laparotomy; and 4) radiation followed by laparotomy. Expanded polytetrafluoroethylene (ePTFE) tubes were implanted subcutaneously in the abdominal wall in the radiotherapy field and on the back outside the radiotherapy field day 0. The abdomen (3 cm x 4 cm) was irradiated day 3 (10 Gy) and again day 7 (10 Gy). On day 10, implants were extirpated, laparotomy undertaken in groups 2 and 4 and new ePTFE tubes implanted subcutaneously. The second implants were extirpated on day 20. Implants were analyzed for hydroxyproline, total protein and transforming growth factor-beta1 (TGF-beta1) levels.


RESULTS
On day 10, hydroxyproline (P < 0.05) and TGF-beta1 (P < 0.001) were lower in ePTFE tubes in irradiated compared with non-irradiated rats. On day 20, the abdominal ePTFE hydroxyproline remained low (P < 0.001) in animals subjected to laparotomy and pre-operative irradiation while hydroxyproline levels of rats subjected to irradiation only were similar to controls. The effects of radiation on hydroxyproline were confined to the irradiated abdominal area. There was a positive correlation between hydroxyproline and TGF-beta1 levels in the abdominal wall implant day 20 (r = 0.53, P < 0.005).


CONCLUSIONS
A clinically relevant fractionated radiation scheme reduced subcutaneous collagen accumulation pre-operatively and profoundly within the radiation field post-operatively after laparotomy, possibly because of lowered TGF-beta1 levels.
Johnson
Louis B
LB
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden. Louis.Johnson@med.lu.se
Adawi
Diya
D
Agren
Magnus S
MS
Jorgensen
Lars N
LN
Wittgren
Lena
L
Mattsson
Sören
S
Blomquist
Peter
P
Gottrup
Finn
F
Jeppsson
Bengt
B
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000378:metabolism; D007813:Laparotomy; D008297:Male; D011138:Polytetrafluoroethylene; D011183:Postoperative Complications / Q000378:metabolism; D011300:Preoperative Care; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000528:radiation effects
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D011138:Polytetrafluoroethylene; D003094:Collagen; D006909:Hydroxyproline