INTRAOPERATIVE IRRADIATION PROLONGS THE PRESENCE OF MATRIX METALLOPROTEINASE ACTIVITY IN LARGE-BOWEL ANASTOMOSES OF THE RAT

There exists a growing interest in intra-operative radiation therapy a s a treatment modality for large bowel cancer. In a previous experimen tal study we showed that high-dose intraoperative irradiation delays t he healing of colonic anastomoses. However, the contribution of protea ses is unknown. In the present study, the gelatinolytic and collagenol ytic activity in the healing anastomoses is investigated. After a rese ction of a I-cm length of colon (uninjured colon), the rats were irrad iated with a single dose of 25 Gy, either to the proximal limb, referr ed to as the proximal group, or to both proximal and distal limbs of t he bowel, referred to as the combined group, before anastomotic constr uction. Both groups were compared to a control group with anastomoses which were sham-irradiated. The animals were killed 1, 3 or 7 days aft er operation. The gelatinolytic activity in uninjured and anastomotic tissue was quantified by gelatin zymography and the collagenolytic act ivity by an assay using a fibrillar rat collagen substrate. Compared w ith resected uninjured colon, most of the gelatinolytic activities wer e markedly increased in anastomotic tissue of all groups during the fi rst postoperative week, and new additional activities were detected. T he additional metalloproteinases (the 95-kDa family) of both irradiate d groups were significantly elevated compared to the anastomoses of th e sham-irradiated control group al 7 days after operation. In anastomo tic tissue of all groups, the collagenolytic activity of the tissue wa s also significantly increased at 1 and 3 days after construction with respect to the resected, uninjured colon. After 7 days this effect ha d disappeared for the sham-irradiated anastomoses, but the activity in the anastomoses in both the proximal and combined groups remained sig nificantly elevated. The findings provide evidence that intra-operativ e irradiation prolongs the presence of elevated gelatinolytic and coll agenolytic activities in colon anastomoses. It may contribute to a red uced or delayed accumulation of collagen and other matrix proteins tha t supply anastomotic strength. (C) 1997 by Radiation Research Society.