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Study on Molecular Analysis and Chemoprevention of Oral Carcinogenesis Using a Rat Oral Carcinogenesis Model

利用大鼠口腔癌模型进行口腔癌的分子分析和化学预防研究

基本信息

批准号：
05671568
负责人：
TANAKA Takuji
金额：
$ 1.22万
依托单位：
Gifu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

To clarify carcinogenesis process of oral cancer and to prevent this cancer, molecular analysis and search of chemopreventive agents against oral carcinogenesis were done using a 4-nitroquinoline 1-oxide (4-NQO)-induced rat oral carcinogenesis model. The results obtained were as follows : 1.Molecular analysis using PCR-SSCP technique revealed infrequent Ha-ras and absence of Ki-ras, N-ras, and p53 mutations in 4-NQO induced rat oral lesions. 2.Histological studies revealed mutistep nature of 4-NQO-induced oral carcinogenesis and strong expression of GGT and GST-P or weakly positive for c-myc, c-fos, c-Ha-ras, c-erbB,p53 in the lesions. 3.Protocatechuic acid (PCA), hesperidin, curcumin, 1'-acetoxychavicol acetate, beta-carotene, astaxanthin, and canthaxanthin effectively suppressed rat oral carcinogenesis. 4.Indole-3-carbinol could inhibit spontaneous endometrial cancer development as well as oral and liver cell neoplasms. 5.PCA,astaxanthin, and canthaxanthin could also inhibit other organs' tumorigenesis (colon, liver, stomach, and bladder) in rats. 6.KYN-54 and mofarotene prevented rat oral carcinogenesis. 7.PCA had anti-progression effects on rat oral carcinogenesis. 8.These results may indicate that all tested compounds are possible chemopreventive agents against oral cancer. Although inhibition in cell proliferation activity in the oral mucosa might be suspected, further studies on the precise mechanisms of inhibition should be done.

为了阐明口腔癌的发生过程，预防口腔癌，采用4-硝基喹啉- 1-氧化物（4-NQO）诱导的大鼠口腔癌模型，进行了分子分析和寻找口腔癌化学预防剂。实验结果如下：1。利用PCR-SSCP技术进行分子分析，发现在4-NQO诱导的大鼠口腔病变中Ha-ras少见，Ki-ras、N-ras和p53缺失。2.组织学研究表明，4- nqo诱导的口腔癌变具有多步性，病变中GGT、GST-P表达强烈或c-myc、c-fos、c-Ha-ras、c-erbB、p53弱阳性。3.原儿茶酸（PCA）、橙皮苷、姜黄素、1′-乙酰氧基chavicol醋酸酯、β -胡萝卜素、虾青素和角黄素可有效抑制大鼠口腔癌的发生。4.吲哚-3-甲醇可抑制自发性子宫内膜癌的发展，并可抑制口腔和肝细胞肿瘤。5.PCA、虾青素、角黄素对大鼠其他器官（结肠、肝脏、胃、膀胱）的肿瘤发生也有抑制作用。6.KYN-54和mofarotene对大鼠口腔癌有预防作用。7.PCA对大鼠口腔癌有抗进展作用。8.这些结果可能表明所有被测试的化合物都可能是口腔癌的化学预防剂。虽然可能怀疑对口腔黏膜细胞增殖活性有抑制作用，但对其抑制的确切机制还有待进一步研究。