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Studies on cigarettes smoke carcinogenesis using trensgenic mouse with human c-Ha-ras gene contained somatically activated transgenes.

使用含有体细胞激活转基因的人类 c-Ha-ras 基因的trensgenic小鼠对香烟致癌进行了研究。

基本信息

批准号：
07670473
负责人：
MATUKI Hideaki
金额：
$ 0.38万
依托单位：
Tokai University Junior College of Nursing and Medical Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Relationship between passive smoking and human lung cancer by epidemiologicalsurvy have been reported. On the other hand, the relation was not clear by inhalation experiment of cigarette smoke to animal. Transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 60% of transgenicoffspring had tumor with 18 months. The aim of this investigation is effected or not effected on somatic mutation and tumor of cigarette smoke using transgenic mice with human c-Ha-ras gene contained. First and second experiment ; Transgenic mice and non-transgenic mice were exposed main stream of cigarette 'smoke which was 10 or 5 times dilluted with fresh air. This study were conducted that 20 cigarettes smoke were exposed in 3 days per week. The difference of mice weight between cigarette smoke exposed group and non-exposed group were not shown. Malignant tumor was not observed both transgenic and non-transgenic mouse in cigarette exposure groups. Third experiment ; Transgenic mice were exposed with 80 cigarettes smoke in 3 days per week. Adenocarcinoma was observed in the lung of one of exposed transgenic mouse. And two non-exposed transgenic mice were also observed adenocarcinoma in the lungs. These malignant tumor were analyzed using PCR followed by oligonucleotide hybridization. As a result, c-Ha-ras genes wre observed in these three lungs.

被动吸烟与人类肺癌的关系已有流行病学报道。另一方面，香烟烟雾对动物的吸入实验表明，两者之间的关系尚不明确。建立了携带人c-Ha-ras杂合基因的转基因小鼠系，其启动子区域编码原型产物。在这些品系中，大约60%的转基因后代在18个月大时患上了肿瘤。本研究的目的是利用含有人c-Ha-ras基因的转基因小鼠，对香烟烟雾的体细胞突变和肿瘤产生影响或不影响。第一次和第二次实验：转基因小鼠和非转基因小鼠暴露于香烟主流烟雾，其中香烟烟雾是新鲜空气的10倍或5倍。这项研究是在每周3天内接触20支香烟烟雾。香烟烟雾暴露组与非香烟烟雾暴露组小鼠体重差异无统计学意义。香烟染毒组转基因小鼠和非转基因小鼠均未观察到恶性肿瘤。第三个实验：转基因小鼠每周三天暴露于80支香烟烟雾中。在其中一只暴露的转基因小鼠的肺中观察到腺癌。而两只未暴露的转基因小鼠也观察到了肺腺癌。用聚合酶链式反应和寡核苷酸杂交法对这些恶性肿瘤进行分析。结果在三个肺中观察到c-Ha-ras基因。