Lorenz and Stewart were the first to induce carcinomas in the colon of rodents (1). Since then, many workers have investigated the morphological, biological and molecular characteristics of colonic adenomas and carcinomas in mice and rats evoked by dimethylhydrazine (DMH) or by its metabolites (azoxymethane and methylazoxymethanol) (2) by spontaneous mutations (3) or genetic manupulations (4).In more recent years, several histological classifications of experimentally-induced colonic adenomas in rats have been proposed (5-13). Some researchers classify adenomas into tubular, villous and a mixed phenotype and tubulo-villous, others into adenomas with mild, moderate and severe dysplasia, and a third group regard adenomas as only those exhibiting severe dysplasia. Similarly, some authors classify invasive carcinomas into well-, moderately and poorly differentiated, and signet-ring cell carcinomas; others into tubular, mucinous, signet-ring cell and undifferentiated; and by a third group into scirrhous, tubular, papillary, tubular-papillary, mucinous, signetring, solid, undifferentiated, and mixed types (5-13). In contrast, Deschner (14), Maskens (15) and, more recently, Ward and Treuting (16) have asserted that adenocarcinomas often develop de novo, and not from adenomas, therefore, adenomas were not histologically classified.Despite the disparate classifications of colonic neoplasias in rodents, the general view has been that colonic carcinomas evolve from conventional (tubular, tubulo-villous or villous) adenomas (5-13). However, recent studies have disclosed additional histological phenotypes of colonic adenomas and carcinomas in DMH-treated Sprague-Dawley (SD) rats (17-19) as follows.
Serrated adenomas and serrated carcinomas.Following activation of a KrasG12D mutant allele or inactivated Apc alleles, Feng et al. (3) found epithelium to be hyperplastic and serrated morphological features in the mouse colon, and Bongers et al. (4) found that transgenic expression of the epidermal growth factor receptor in conjunction with ligand heparin-binding epidermal growth factor in mice promoted caecal serrated polyps, but not serrated adenomas. Recently in 215 DMH-treated SD rats, tumours were found to be 1% serrated adenomas, 8% microtubular adenomas, 3% serrated carcinomas and 3% microtubular carcinomas (19). Thus, serrated adenomas and serrated carcinomas can be evoked in 6667 This Αrticle is freely accessible online.