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，使用4-硝基醇1-氧化物（4-NQO）诱导的大鼠口服癌变模型进行了分子分析和针对口服癌变的化学预防剂的搜索。所获得的结果如下：1。使用PCR-SSCP技术分析表明，在4-NQO诱导的大鼠口服病变中，不经常HA-RAS和Ki-Ras，N-Ras和p53突变的不存在。 2.组织学研究揭示了4-NQO诱导的口服致癌作用以及GGT和GST-P的强烈表达，或者在病变中C-Myc，C-Fos，C-HA-RAS，C-ERBB，p53的弱阳性。 3.促磷酸酸（PCA），黄质蛋白，姜黄素，1'-乙酰氧基乙酸乙酸酯，β-胡萝卜素，虾青素和canthaxanthin有效地抑制了大鼠口腔癌变。 4. Indole-3-甲醇可以抑制自发的子宫内膜癌发展以及口腔和肝细胞肿瘤。 5.pca，astaxanthin和canthaxanthin也可以抑制大鼠其他器官的肿瘤发生（结肠，肝脏，胃和膀胱）。 6.Kyn-54和mofarotene阻止了大鼠口腔癌变。 7.PCA对大鼠口腔癌变产生抗突出作用。 8.这些结果可能表明所有测试化合物都是针对口腔癌的化学预防剂。尽管可能会怀疑口腔粘膜中细胞增殖活性的抑制作用，但应进一步研究抑制的精确机制。