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

为了阐明口腔癌的发生过程，预防口腔癌的发生，采用4-硝基喹啉-1-氧化物(4-NQO)诱导的大鼠口腔癌模型，进行了口腔癌化学预防药物的分子分析和研究。结果如下：1.应用PCR-SSCP技术进行分子生物学分析，发现4-NQO诱导的大鼠口腔病变中Ha-ras基因罕见，Ki-ras、N-ras和P53基因突变缺失。2.组织学观察发现，4-NQO诱发口腔癌具有多步骤的特点，病变中GGT、GST-P呈强阳性表达，而c-myc、c-fos、c-Ha-ras、c-erbB、P53呈弱阳性表达。3.原儿茶酸(PCA)、橙皮苷、姜黄素、1‘-乙酰氧基茶酚乙酸酯、β-胡萝卜素、虾青素、角黄素能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、虾青素和角黄素对大鼠其他器官(结肠、肝、胃、膀胱)的成瘤也有抑制作用。6.KYN-54和莫法罗汀预防大鼠口腔癌的发生。7.苦参碱对大鼠口腔癌变具有抗癌作用。8.这些结果可能表明所有受试化合物都可能是预防口腔癌的化学预防药物。虽然怀疑口腔粘膜中的细胞增殖活性受到抑制，但对其确切的抑制机制仍需进一步研究。

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.