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 beta-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 beta-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.
Yoshimi
Naoki
N
Tumor Pathology, University of the Ryukyus Faculty of Medicine, Uehara Nishihara-cho, Okinawa 903-0215, Japan. yoshimi@med.u-ryukyu.ac.jp
Morioka
Takamitsu
T
Kinjo
Tatsuya
T
Inamine
Morihiko
M
Kaneshiro
Tatsuya
T
Shimizu
Takahiro
T
Suzui
Masumi
M
Yamada
Yasuhiro
Y
Mori
Hideki
H
D019813:1,2-Dimethylhydrazine; D000423:Alcian Blue; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D009077:Mucins / Q000032:analysis*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling / Q000379:methods; D015534:Trans-Activators / Q000032:analysis; D051176:beta Catenin
D014408:Biomarkers, Tumor; D002273:Carcinogens; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D009077:Mucins; D015534:Trans-Activators; D051176:beta Catenin; D019813:1,2-Dimethylhydrazine; D000423:Alcian Blue