抄録
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.
