Cell kinetics and polyamine enzymes in the intestinal mucosa of rats with azoxymethane induced tumours.

ABSTRACT

We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal 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 extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher 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 +/- 0.02, P < 0.001; left colon 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of 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 was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)