Related Experiment Video
Updated: Jun 12, 2026
Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
Early lesions induced in rat colon epithelium by N-methyl-N'-nitro-N-nitrosoguanidine
T C H Che1, S François, S Bouchet
1INSERM and UPMC, UMR-S 938, Team Biology and Therapeutics of Cancer, Centre de Recherches Paris Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France.
Abstract:
The development of ACF (aberrant crypt foci), adenoma and cancer following intrarectal administration of the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) has been described. However, microscopic lesions not previously reported were observed as soon as two weeks following carcinogen treatment. These lesions protrude slightly over the epithelial lining of the colon, with a micropolyp-like appearance. Oriented sections show that the centre of these lesions present pseudo-"cystic" appearance, with disorganized crypts made of normal cells. The chorion of the lesion is invaded by numerous inflammatory cells and some ACF may be present nearby. The epithelium lining the cysts and the distorted crypts shows expression of gastric mucin M1/MUC5AC, an early marker of colonic carcinogenesis which is not present in normal colon. This mucin is retained within the "cysts" together with some inflammatory cells. The micropolyps observed contain in a minute form some histological elements described in ulcerative colitis or short-term radiotherapy (distortion of crypts, crypt abscesses, increase of chorion cellularity, infiltration by immune cells). In addition, the presence of bifid crypts nearby suggests mucosal regeneration. Our hypothesis is that these modifications are steps in a normal healing pathway that may in some cases degenerate into precancerous lesions and cancer.
Insights
Early colonic lesions, resembling healing responses, were observed after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) exposure. These microscopic changes may represent precancerous steps in the development of colon cancer.
Area of Science:
- Gastroenterology
- Oncology
- Pathology
Background:
- Aberrant crypt foci (ACF), adenoma, and cancer development after N-methyl-N itro-N-nitrosoguanidine (MNNG) administration are established. However, earlier microscopic changes were not well-characterized.
- The early stages of chemically induced colorectal carcinogenesis are crucial for understanding disease progression.
Purpose of the Study:
- To characterize novel microscopic lesions observed early after MNNG administration in the colon.
- To investigate the potential role of these lesions as precursors in the pathway to colonic precancerous lesions and cancer.
Main Methods:
- Intrarectal administration of the alkylating agent N-methyl-N itro-N-nitrosoguanidine (MNNG) to induce colonic lesions.
- Histological examination of colon tissue at two weeks post-treatment to identify and characterize microscopic lesions.
- Immunohistochemical analysis to detect the expression of gastric mucin M1/MUC5AC.
Main Results:
- Newly observed microscopic lesions with a micropolyp-like appearance were identified as early as two weeks after MNNG treatment.
- These lesions featured pseudo-cystic centers with disorganized crypts, inflammatory cell infiltration, and expression of gastric mucin M1/MUC5AC, an early marker of carcinogenesis.
- Histological similarities were noted between these micropolyps and features of ulcerative colitis or radiotherapy, alongside evidence of mucosal regeneration (bifid crypts).
Conclusions:
- The observed microscopic lesions represent early changes in the colon following MNNG exposure.
- These lesions exhibit characteristics suggestive of a healing response that may, in some instances, progress to precancerous lesions and ultimately cancer.
- Gastric mucin M1/MUC5AC expression in these early lesions indicates a potential role in the initial stages of colonic carcinogenesis.
