Point Mutations of the c-H-ras Gene in Spontaneous Pulmonary Tumors of Transgenic Mice Carrying the Human c-H-ras Gene

概要

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Spontaneous proliferative pulmonary lesions were found in 10 (6 males and 4 females) of 244 (122 of each sex) transgenic (Tg) mice carrying the human prototype c-H-ras gene (rasH2). The pulmonary lesions included 2 bronchiolo-alveolar hyperplasias (BAHs), 2 bronchiolo-alveolar adenomas (BAAs), and 2 bronchiolo-alveolar adenocarcinomas (BACs) in males and 1 BAH and 3 BACs in females. The mutation patterns of the human c-H-ras codon 61 and endogenous mouse c-K-ras codons 12, 13, and 61 in these proliferative pulmonary lesions were analyzed by DNA amplification using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP), and oligonucleotide dot blot hybridization. Two of the 3 BAHs, 1 of the 2 BAAs, and 5 of the 5 BACs had a CAG to CTG transversion at codon 61 of the human c-H-ras gene but no point mutations were detected in codons 12, 13, or 61 of the mouse c-K-ras gene. Immunohistochemically, no overexpression of p53 protein, hsp70 or mdm2 gene protein was detected in any of the lesions. These findings suggest that, at least, a point mutation of the human c-H-ras transgene may be an important step in progression of spontaneous lung tumors, whereas p53 abnormality may not play an important role of the pulmonary carcinogenesis in rasH2 Tg mice.
日本毒性病理学会の論文
1999-12-01