SHINDOH Masanobu SCHOOL OF DENTISTRY,HOKKAIDO UNIVERSITY,ASSOCIATE PROFESSOR, 歯学部, 助教授 (20162802)
CHIBA Itsuo SCHOOL OF DENTISTRY,HOKKAIDO UNIVERSITY,INSTRUCTOR, 歯学部, 助手 (50250460)
|Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥5,500,000 (Direct Cost: ¥5,500,000)
Carcinogenesis is a multistep process, and thus an accumulation of several independent genetic abnormalities is necessary for the progression of cancer. Recent research on genetic alterations found in human cancers has shown that activation of oncogenes and inactivation of tumor suppressor genes are major steps in the development of cancers. Mutations of the p53 gene have also been observed in a variety of non-invasive, dysplastic epithelial lesions from various tissues, including oral cavity, esophagus, and lung. Since premalignant legions could be genetically heterogenous, it is necessary to use sensitive methods for detecting mutations in a small population. Because of this background, we analyzed genetic changes occurring in human oral SCC and premalignant lesions in Japan and Sri Lanka, which were caused by betel chewing, to clarify specific genetic events for promoting premalignant lesion to cancer (Oncogene, 15 : 2667, 1997., The 90th Annual Meeting of American Association for Cancer Research). In addition, we used DMBA-induced hamster cheek pouch carcinogenesis model to analyze mutations in the p53 and ras genes chronologically (Jpn. J.Oral Maxillofac. Surgery, 42 : 347, 1996., ibid, 44 : 925, 1998.). The following methods were applied ; 1) MASA (mutant allele specific amplification), 2) yeast functional assay, and 3) analysis of microsatellite alteration. Mutations in the p53 gene, the ras gene and microsatellite alterations occurred not only in cancers but also in premalignqant lesions in both animal model and human cases. Our data suggest that genetic changes could occur during premalignant stages and it is important to have preventive strategies during these stages.