Frequent mutations of Ki-ras but no mutations of Ha-ras and p53 in lung lesions induced by N-nitrosobis(2-hydroxypropyl)amine in rats

✍ Scribed by Hiromichi Kitada; Masahiro Tsutsumi; Toshifumi Tsujiuchi; Makoto Takahama; Tomokazu Fukuda; Nobuhiro Narita; Yoichi Konishi

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 591 KB
• Volume: 15
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199604)15:4<276::aid-mc5>3.0.co;2-e

✦ Synopsis

Point mutations of the Ki-ras andp53 genes in rat lung lesions induced by N-nitrosobis(2-hydroxypropy1)amine (BHP) were investigated by polymerase chain reaction-single-strand conformation polymorphism analysis followed by direct sequencing using paraffin-embedded tissues. Male Wistar rats 6 wk old were given 2000 ppm BHP in drinking water for 15 wk. Another group was given drinking water without BHP. The rats were killed 20-27 wk after the beginning of the experiment. Lung adenomatous and squamous lesions, including carcinomas, were induced. The frequencies of Ki-ras mutations were 40% (six of 15) in alveolar hyperplasias, 36% (five of 14) in adenomas, 72% (18 of 25) in adenocarcinomas, 20% (three of 15) in squamous metaplasias, 50% (three of six) in squamous cell carcinomas, and 50% (five of 10) in adenosquamous carcinomas. The mutations were all G --;r A transitions at the second position of codon 12; no other mutations were detected. However, Haras mutations in exons l and 2 and p53 mutations in exons 5, 6, and 7 were not detected in adenocarcinomas and squamous cell carcinomas. These results indicate that Ki-ras mutation is an early genetic event in some adenomatous and squamous lung carcinogeneses and that Ki-ras mutations can cause benign lesions to convert to malignant lesions. The results also show that Ha-ras and p53 mutations are not involved in rat lung carcinogenesis induced by BHP.