Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis.
Our previous study (Cancer Res., 60: 3323-3327, 2000) showed that frequent beta-catenin gene mutations are present in beta-catenin-accumulated crypts, which occur early in rodent colonic carcinogenesis, with a lack of the appearance of aberrant crypt foci (ACF). To clarify the nature of such lesions, we performed a sequential analysis of the morphological and biological properties of beta-catenin-accumulated crypts. Azoxymethane was administered s.c. to male F344 rats (15 mg/kg body weight) once a week for 3 weeks, and the animals were sacrificed at 5, 10, and 20 weeks after the carcinogen treatment. Both the number of crypts/lesion and the diameter of beta-catenin-accumulated crypts were significantly increased with time courses of 5, 10, and 20 weeks from carcinogen exposure (P < 0.01). Likewise, the histological abnormality in those crypts, assessed by semiquantitative analyses, was also increased with time (P < 0.01). Conversely, ACF did not show any increase in histological abnormality during the time course and maintained a monotonous histology throughout the experiment. The histological abnormality score for beta-catenin-accumulated crypts was significantly higher than for ACF at every time point (P < 0.001). The number of AgNOR/nucleus in beta-catenin-accumulated crypts was significantly higher than in ACF (P < 0.001). Beta-catenin-accumulated crypts were accompanied frequently by Paneth cells and had decreased hexosaminidase activity. Such data, together with the results in our previous report, strongly suggest that beta-catenin-accumulated crypts, which are independent of ACF, are truly premalignant lesions for colon cancer.
Department of Pathology, Gif University School of Medicine, Japan. y-yamada@cc.gifu-u.ac.jp
Y
Y
Yamada
N
N
Yoshimi
Y
Y
Hirose
K
K
Matsunaga
M
M
Katayama
K
K
Sakata
M
M
Shimizu
T
T
Kuno
H
H
Mori
D000818:Animals; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D009697:Nucleolus Organizer Region / Q000378:metabolism; D011230:Precancerous Conditions / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D016622:Silver Staining; D015534:Trans-Activators; D051176:beta Catenin; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D001619:beta-N-Acetylhexosaminidases