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，本研究利用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剂的分子分析和研究。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。

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.