Preliminary analysis of azoxymethane induced colon tumors in inbred mice commonly used as transgenic/knockout progenitors.
Preliminary analysis of azoxymethane induced colon tumors in inbred mice commonly used as transgenic/knockout progenitors.
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DOI：
10.3892/ijo.22.1.145
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发表时间：
2003
影响因子：
5.2
通讯作者：
P. Nambiar;G. Girnun;Nicholas A Lillo;K. Guda;H. Whiteley;D. Rosenberg
中科院分区：
文献类型：
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作者：
P. Nambiar;G. Girnun;Nicholas A Lillo;K. Guda;H. Whiteley;D. Rosenberg
氧化偶氮甲烷（AOM）是一种结肠致癌物，用于研究散发性结直肠癌的发病机制。我们已经评估了作为重组/转基因系的祖细胞的近交系小鼠对AOM的不同易感性。在实验1中，雄性FVB/N、129/SvJ、C57 Bl/6 J小鼠每周一次腹腔注射10 mg/kg AOM，持续4周，20周后处死。仅AOM处理的FVB/N小鼠在远端结肠中产生肿瘤（3.6个肿瘤/小鼠）。实验2中，A/J、AKR/J、Balb/CJ小鼠用AOM处理6周，24周后处死。AOM处理的A/J和Balb/CJ小鼠分别产生9.2和1个肿瘤/小鼠。尽管存在这些差异，但无论菌株如何，肿瘤具有相似的形态。β-连环蛋白免疫组化显示FVB/N中肿瘤细胞的细胞核和细胞质染色明显。然而，在A/J肿瘤中观察到较弱和不均匀的β-连环蛋白染色，表明不同菌株中肿瘤发生的不同途径。无论恶性肿瘤的细胞学特征如何，肿瘤细胞很少突破粘膜肌层，也没有远处转移的证据。即使是最敏感的菌株也缺乏侵袭性和转移性，这为研究“转移基因”在赋予恶性表型中的潜在作用提供了模型系统。
Azoxymethane (AOM) is a colon carcinogen that is used to study the pathogenesis of sporadic colorectal cancer. We have evaluated differential susceptibility to AOM in inbred mice used as progenitors of recombinant/transgenic lines. In experiment 1, male FVB/N, 129/SvJ, C57Bl/6J mice were treated i.p. with 10 mg/kg AOM once per week for 4 weeks and sacrificed after 20 weeks. Only AOM-treated FVB/N mice developed tumors (3.6 tumors/mouse) in distal colon. In experiment 2, A/J, AKR/J, Balb/CJ mice were treated with AOM for 6 weeks and sacrificed after 24 weeks. AOM-treated A/J and Balb/CJ mice developed 9.2 and 1 tumor/mouse, respectively. Despite these differences, tumors had similar morphology regardless of strain. Immunohistochemistry with beta-catenin resulted in marked nuclear and cytoplasmic staining of tumor cells in FVB/N. However, fainter and heterogeneous beta-catenin staining was observed in A/J tumors, suggesting distinct pathways of tumorigenesis in different strains. Irrespective of cytological features of malignancy, tumor cells rarely breached the muscularis mucosa and showed no evidence of distant metastasis. Lack of invasiveness and metastasis in even the most sensitive strains provides a model system for studying the potential role of 'metastasis genes' in imparting a malignant phenotype.