Histological and immunohistochemical observations of mucin‐depleted foci (MDF) stained with Alcian blue, in rat colon carcinogenesis induced with 1,2‐dimethylhydrazine dihydrochloride

The usefulness of mucin‐depleted foci (MDF), which have recently been proposed as a new preneoplastic biomarker in rat colon carcinogenesis, was histologically investigated in rat colonic tissues treated with 1,2‐dimethylhydrazine dihydrochloride (DMH). The relationship among aberrant crypt foci (ACF), MDF and β‐catenin accumulated crypts (BCAC) was examined by comparing the corresponding computer‐captured images. Twelve male F344 rats were given DMH s.c. at a dose of 40 mg/kg body weight, once a week for 2 weeks, and randomly divided into two groups. Rats in group 1 were given normal drinking water, while those in group 2 were given drinking water containing indomethacin (IND) at 16 ppm for 6 weeks. All animals were sacrificed 8 weeks after the first DMH treatment. The resected colons were fixed in 10% formalin, and stained with Alcian blue for observation of ACF and MDF. Histological and immunohistochemical analysis revealed that the numbers of ACF, MDF and overlapping lesions in group 2 (treated with IND) were significantly decreased, compared with those in group 1. The number of BCAC in group 2 was also significantly lower than that in group 1. The reduction (61.5%) of MDF by IND was much greater than that (29.3%) of ACF. Analyses of the computer‐captured images indicated that MDF had more frequent dysplastic changes and overexpression of β‐catenin than did ACF. MDF having over 4 crypts or MDF with the appearance of ACF corresponded well to BCAC. These results suggest that MDF may be useful as an early biomarker in colon carcinogenesis.

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