Azoxymethane-induced colorectal tumorigenesis in hypertensive rat models

To compare the tumor susceptibility between the hypertensive Dahl salt-sensitive rats (S) rat and S.LEW(10)x12x2x3x5 (S.LEW) congenic strain, one of the S.LEW congenic strains our laboratory previously constructed on rat chromosome 10 [Hypertension. 2007 Nov;50(5):891-8], Azoxymethane (AOM)-induced colon tumorigenesis in rats was assessed. At six weeks of age, both S and S.LEW congenic rats received intraperitoneal (IP) injection of AOM in sterial saline at a dose of 15mg/kg body weight once a week for two consecutive weeks. At 30 weeks of age, all the rats were euthanized through carbon dioxide inhalation. The colon tissue was harvested, dissected longitudinally, and washed with saline. The number and size of the colon tumors were recorded. We found that the total number of colon tumors was significantly higher in the S.LEW congenic strain compared with the S rat. To further study the genetic and molecular mechanisms causing the higher tumor susceptibility in the S.LEW congenic strain, we have employed the whole genome microarray expression profiling to identify genes and signaling pathways that are differential between the S and S.LEW congenic strain.为比较高血压型Dahl盐敏感大鼠（S大鼠）与本实验室此前在大鼠10号染色体上构建的S.LEW同类系（S.LEW(10)x12x2x3x5，简称S.LEW）的肿瘤易感性差异——该同类系相关研究已发表于《Hypertension》2007年11月，第50卷第5期，第891-8页——，本研究评估了偶氮甲烷（Azoxymethane, AOM）诱导的大鼠结肠肿瘤发生情况。于6周龄时，S大鼠与S.LEW同类系大鼠均接受腹腔注射（intraperitoneal, IP）：以无菌生理盐水配制的AOM，剂量为15mg/kg体重，每周1次，连续给药2周。至30周龄时，所有大鼠经二氧化碳吸入法实施安乐死，随后采集结肠组织，纵向剖开并以生理盐水冲洗，记录结肠肿瘤的数量与大小。结果显示，相较于S大鼠，S.LEW同类系的结肠肿瘤总数量显著更高。为进一步探究导致S.LEW同类系肿瘤易感性升高的遗传与分子机制，本研究采用全基因组微阵列表达谱分析，以鉴定S大鼠与S.LEW同类系之间存在表达差异的基因及信号通路。