Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis.
Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis.
复制标题
对β-连环蛋白积累的隐窝的形态学和生物学特性进行连续分析，证明癌前病变与大鼠结肠癌发生中的异常隐窝病灶无关。
作者：
Yasuhiro Yamada;Naoki Yoshimi;Y. Hirose;K. Matsunaga;M. Katayama;K. Sakata;Masahito Shimizu;T. Kuno;Hideki Mori
我们之前的研究（Cancer Res., 60: 3323-3327, 2000）表明，β -连环蛋白积累的隐窝中存在频繁的β -连环蛋白基因突变，这种突变发生在啮齿动物结肠癌变的早期，缺乏异常隐窝灶（ACF）的出现。为了阐明这种病变的性质，我们对β -连环蛋白积累的隐窝进行了形态学和生物学特性的序列分析。雄性F344大鼠每周1次按15 mg/kg体重给药偶氮氧甲烷，连续给药3周，于致癌物处理后5、10、20周处死。暴露5周、10周和20周后，隐窝/病变数量和β -连环蛋白积累的隐窝直径均显著增加（P < 0.01）。半定量分析显示，随着时间的延长，隐窝组织异常程度也增加（P < 0.01）。相反，ACF在时间过程中没有表现出任何组织学异常的增加，并且在整个实验过程中保持单调的组织学。各时间点β -连环蛋白积累隐窝的组织学异常评分均显著高于ACF （P < 0.001）。β -连环蛋白积累的隐窝中AgNOR/细胞核数量显著高于ACF （P < 0.001）。β -连环蛋白积累的隐窝经常伴有Paneth细胞，并且己糖氨酸酶活性降低。这些数据，连同我们之前报告的结果，强烈提示β -连环蛋白积累的隐窝，独立于ACF，是真正的结肠癌癌前病变。
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.
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金雀异黄素增强实验性结肠癌。
DOI：
--
发表时间：
1997
期刊：
Cancer research.
影响因子：
--
作者：
Rao,CV;Wang,CX;Simi,B;Lubet,R;Kelloff,G;Steele,V;Reddy,BS
通讯作者：
Reddy,BS
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
DOI：
--
发表时间：
1993-06
期刊：
The American journal of pathology
影响因子：
--
作者：
X. Tan;W. Hsueh;F. Gonzalez‐Crussi
通讯作者：
X. Tan;W. Hsueh;F. Gonzalez‐Crussi
类视黄醇对 AOM 诱导的大鼠结肠癌的影响：细胞增殖、凋亡和异常隐窝病灶的调节。
影响因子：
4.7
作者：
Zheng,Y;Kramer,PM;Lubet,RA;Steele,VE;Kelloff,GJ;Pereira,MA
通讯作者：
Pereira,MA
通过用致癌物质处理的 F344 大鼠的整个结肠中己糖胺酶活性鉴定出两种类型的推定肿瘤前病变。
DOI：
--
发表时间：
1993
期刊：
The American journal of pathology
影响因子：
--
作者：
Pretlow,TP;O'Riordan,MA;Spancake,KM;Pretlow,TG
通讯作者：
Pretlow,TG