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I I I I I I I I I I I I I I I I ANALYSIS OF P53 AND K-RAS MUTATIONAL PATTERNS IN LUNG CANCER Gao Hong-gran~2*, Chen 7ia-kun**, Wu Zhong-liang**, Whong Wen-zong* and Ong Tong-man* * Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA ** Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou, China Lung cancer is the most prevalent cancer in the world. The mechanism of lung carcinogenesis is not really known. Studies have been conducted to examine the mutational spectra of K-ras exons 1-2 and p53 exons 5-8 in lung cancer tissues from 27 Chinese patients (10 smokers and 17 nonsmokers) using single strand conformational polymorphism (SSCP) and DNA sequencing. Results show that K-ras mutations were found in 11 of 13 squamous cell carcinomas and 4 of 12 adenocarcinomas. All of the mutations were concentrated in exon I and distributed among codons 12-32. In p53, mutations were found in 10 of 13 squamous cell carcinomas and 7 of 12 adenocarcinomas, and were most frequent at codons 275 and 281. Most of the cancer tissues were found to contain multiple mutations in the p53 gene. The mutational spectra in p53 did not appear to be significantly different between smokers and nonsmokers and consisted of AT-TA transversions (64%) and GC-AT transitions. Based on the exons studied, the number of mutations in-these two genes was significantly higher in squamous cell carcinomas than in adenocarcinomas. These results, in part, indicate that cigarette smoking may cause and/or be associated with a specific mutational pattern in the K-ras proto-oncogene. 0 00 , V 00 3 CA I