Effects of ovariectomy on microsatellite instability in rat colon tumors induced by 1,2-dimethylhydrazine
Effects of ovariectomy on microsatellite instability in rat colon tumors induced by 1,2-dimethylhydrazine
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DOI：
10.1007/s11033-009-9523-5
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Tang, Shouyuan
中科院分区：
文献类型：
--
作者：
Xu, Fei;Wang, Guobin;Tang, Shouyuan
研究卵巢切除对1，2-二甲基肼诱导的大鼠结肠肿瘤发生和微卫星不稳定性（MSI）的影响，探讨绝经后卵巢激素耗竭与MSI通路在结直肠肿瘤发生中的关系。将40只雌性Wistar大鼠随机分为两组：去卵巢组（Ovx）和假去卵巢组（Sham-Ovx）。所有大鼠腹腔注射1，2-二甲基肼（DMH）（20 mg/kg B.w），每周1次，共20周。最后一次注射DMH后10周，处死所有大鼠以收集肿瘤。采用荧光PCR技术检测6个微卫星位点的微卫星不稳定性，并在全自动DNA测序仪上用GeneScan 3.7软件进行片段分析。OVX组的肿瘤多样性显著高于Sham-OVX组（3.6 +/-A1.4 vs.2.4 +/-A1.6，P < 0.05）。OVX组MSI阳性肿瘤的发生率高于Sham-OVX组（32.1vs. 10.8%，P < 0.05），OVX组多个位点出现MSI的肿瘤发生率也高于Sham-OVX组（18.9vs. 2.7%，P < 0.05）。卵巢切除术增加DMH诱导的结肠肿瘤的肿瘤形成和MSI的频率。提示绝经后卵巢激素耗竭可能通过MSI途径影响结直肠肿瘤的发生。
To study the effects of ovariectomy on tumorigenesis and microsatellite instability (MSI) in rat colon tumors induced by 1,2-dimethylhydrazine, to elucidate the association between postmenopausal ovarian hormones depletion and MSI pathway in colorectal tumorigenesis. Forty female Wistar rats were randomly divided into two groups: Ovariectomized (Ovx) group and Sham-ovariectomized (Sham-Ovx) group. All rats were injected intraperitoneally with 1,2-dimethylhydrazine (DMH) (20 mg/kg b.w) once a week for 20 weeks. Ten weeks after the final DMH injection, all the rats were sacrificed to collect tumors. Microsatellite instability of six microsatellite loci was detected using fluorescent PCR followed by fragment analysis on automatic DNA sequencer with GeneScan 3.7 software. The tumor multiplicity in the OVX group was significantly higher than that in the Sham-OVX group (3.6 +/- A 1.4 vs. 2.4 +/- A 1.6, P < 0.05). The incidence of MSI-positive tumors in OVX group was higher than that in Sham-OVX group (32.1 vs. 10.8%, P < 0.05).The incidence of tumors showing MSI at multiple loci in OVX group was also higher than that in Sham-OVX group (18.9 vs. 2.7%, P < 0.05). Ovariectomy increased tumor formation and the frequency of MSI in DMH-induced colon tumors. It implied that postmenopausal ovarian hormones depletion might influence colorectal tumorigenesis through MSI pathway.