Early lesions induced in rat colon epithelium by N-methyl-N'-nitro-N-nitrosoguanidine.
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.
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INSERM 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.
François
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S
Bouchet
S
S
Chapel
A
A
Forgue-Lafitte
M-E
ME
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D055271:Mucin 5AC / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D008769:Methylnitronitrosoguanidine