CELL-KINETICS AND POLYAMINE ENZYMES IN THE INTESTINAL-MUCOSA OF RATS WITH AZOXYMETHANE-INDUCED TUMORS

We studied the proliferative activity and the modifications in ornithi ne decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of r ats with azoxymethane induced tumours. Fifty rats were treated with si x weekly injections of 15mg/kg body weight azoxymethane (AOM). Six rat s died during the treatment. All the surviving rats developed intestin al tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9 % (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an ex tension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthe sizing cells from the basal region to the middle and upper third (stag e II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly high er than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon. 1.32 +/- 0.34 vs 0.25 +/- 0.0 2, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). W e also detected a significant decrease of DAO activity in the mucosa o f the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon wa s unchanged. The lower incidence of tumours in the small bowel and rig ht colon suggests the presence of factors protecting these segments fr om carcinogenesis. Furthermore, a modified expression of ODC and DAO i s associated with proliferative abnormalities in intestinal epithelial cells.