The adenoma-carcinoma sequence in AMMN-induced colonic tumors of the rat

There is general agreement today that most colorectal carcinomas develop from adenomas via the so-called adenoma-carcinoma-sequence. There has however in addition been a discussion regarding the possibility of carcinomas arising "de-novo". The aim of the present study was to find out alterations preceding carcinomas in animal experiment and to demonstrate possible similarities to man. For colonic tumor induction in 40 male Sprague-Dawley rats the local acting nitrosamine-derivative acetoxymethyl-methylnitrosamine was instilled intrarectally once a week for 6 weeks in a dosage of 2 mg/kg bodyweight. 14 weeks after the end of the tumor induction those 28 animals, that had developed endoscopically recognizable tumors, were randomized into two groups. The animals from group I were sacrificed 3 weeks, the animals from group II 20 weeks later, that is 23 and 40 weeks after the start of the experiment. At histopathologic examination an increase of the number of tumors per animal and a doubling of the mean tumor diameter could be observed in group II. The most severe findings (adenoma, adenoma with dysplasia, carcinoma) were more pronounced in group II. "De-novo" carcinomas without residues of benign adenomas were not found. It could be demonstrated, that chemically induced colonic tumours produced in the way described, develop in a fashion quite similar to the conditions found in man via the adenoma-carcinoma-sequence.