The chronological appearance of flat colonic neoplasias in rats

Following weekly s.c. injections of the colonotropic carcinogen 1,2-dimethylhydrazine (DMH), we investigated the occurrence of flat and protruding neoplasias in the colon of rats at various time intervals. Forty-seven DMH-treated rats were sacrificed at the 13th, 15th, 19th, 21st and 22nd weeks. A total of 88 tumors evolved in 35 of the 47 DMH-treated rats. The number of neoplasias/animal was 0.3 at week 13, 1.2 at week 15, 2.0 at week 19, 2.5 at week 21 and 4.0 at week 22. In the right colon, although the percent of flat adenomas was lower than of protruding adenomas, the percent of flat carcinomas was significantly higher than of protruding carcinomas, indicating that flat adenomas progress more rapidly to invasive carcinoma than protruding adenomas in the right colon. The opposite was recorded in the left colon where the percent of protruding adenomas was lower than of flat adenomas, but the percent of protruding carcinomas was higher than of flat carcinomas. During the last experimental week as many as 63% of the protruding carcinomas occurred but only 25% of the flat carcinomas. These experimental results seem to substantiate previous observations in humans suggesting that, in the colonic mucosa, flat and protruding adenomas follow different pathways of neoplastic transformation.