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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.

为了阐明口腔癌的致癌过程并预防这种癌症，利用4-硝基喹啉1-氧化物（4-NQO）诱导的大鼠口腔癌致癌模型进行了分子分析和寻找抗口腔癌化学预防剂。结果表明：1.应用PCR-SSCP技术，在4-NQO诱导的大鼠口腔粘膜病变中，Ha-ras基因突变较少，Ki-ras、N-ras和p53基因突变均不存在。2.组织学观察显示4-NQO诱发口腔癌的多步骤性，癌组织中GGT、GST-P强表达或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 '-乙酰氧基胡椒酚乙酸酯、β-胡萝卜素、虾青素和黄色素有效地抑制大鼠口腔癌的发生。4.吲哚-3-甲醇对自发性子宫内膜癌、口腔癌和肝细胞癌均有抑制作用。5.PCA、虾青素、三尖杉黄素对大鼠结肠、肝、胃、膀胱等脏器的成瘤均有抑制作用。6.KYN-54和莫法罗汀预防大鼠口腔癌的发生。7.五氯苯甲醚对大鼠口腔癌的发生有抑制作用。8.这些结果可能表明，所有测试的化合物是可能的化学预防剂对口腔癌。虽然可能会抑制口腔粘膜中的细胞增殖活性，但应进一步研究其确切的抑制机制。