BIOMAT Database Logo BIOMAT Database Logo

Pulmonary fibrosis caused by N-methyl-N-nitrosourethane inhibits lung tumorigenesis by urethane in transgenic mice carrying the human prototype c-Ha-ras gene. 1998

K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. mitsumor@nihs.go.jp

Male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and their wild littermates (non-Tg mice) received three subcutaneous injections of 0.3 mg N-methyl-N-nitrosourethane (MNUR) once every 2 weeks for the first 4 weeks followed by a single intraperitoneal injection of 1000 or 0 mg/kg urethane (UR) 2 weeks later. They were then maintained without any other treatment for a further 13 weeks and sacrificed for assessment of pulmonary pathology. Inflammatory lesions, such as macrophage infiltration, alveolar bronchiolization and/or fibrosis, were induced in both rasH2 and non-Tg mice treated with MNUR or MNUR + UR. Lung proliferative lesions were induced in 100% of the UR-treated rasH2 mice but to a significantly lesser extent in the MNUR + UR case. The incidences of lung tumors in non-Tg mice treated with UR or MNUR + UR were relatively low. Point mutations of the transgene were detected in approximately 80% of lung tumors in rasH2 mice treated with UR and MNUR + UR, but murine Ki-ras mutations were rare. No marked difference in the mutation pattern was found between the UR-treated and the MNUR + UR-treated rasH2 mice. In non-Tg mice treated with UR or MNUR + UR, point mutations of the murine c-Ki-ras gene were observed in about 50% of the lung tumors examined. The present study confirmed that rasH2 mice are very sensitive to lung tumor induction by UR and suggested that alveolar epithelial cells in the reparative stage during pulmonary fibrosis are resistant to DNA damage by this carcinogen.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009605 Nitrosomethylurethane An alkylating carcinogen that produces gastrointestinal and probably lung and nervous system tumors. Methylnitrosourethane
D011658 Pulmonary Fibrosis A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death. Alveolitis, Fibrosing,Idiopathic Diffuse Interstitial Pulmonary Fibrosis,Fibroses, Pulmonary,Fibrosis, Pulmonary,Pulmonary Fibroses,Alveolitides, Fibrosing,Fibrosing Alveolitides,Fibrosing Alveolitis
D011905 Genes, ras Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein. Ha-ras Genes,Ki-ras Genes,N-ras Genes,c-Ha-ras Genes,c-Ki-ras Genes,c-N-ras Genes,ras Genes,v-Ha-ras Genes,v-Ki-ras Genes,H-ras Genes,H-ras Oncogenes,Ha-ras Oncogenes,K-ras Genes,K-ras Oncogenes,Ki-ras Oncogenes,N-ras Oncogenes,c-H-ras Genes,c-H-ras Proto-Oncogenes,c-Ha-ras Proto-Oncogenes,c-K-ras Genes,c-K-ras Proto-Oncogenes,c-Ki-ras Proto-Oncogenes,c-N-ras Proto-Oncogenes,ras Oncogene,v-H-ras Genes,v-H-ras Oncogenes,v-Ha-ras Oncogenes,v-K-ras Genes,v-K-ras Oncogenes,v-Ki-ras Oncogenes,Gene, Ha-ras,Gene, Ki-ras,Gene, v-Ha-ras,Gene, v-Ki-ras,Genes, Ha-ras,Genes, Ki-ras,Genes, N-ras,Genes, v-Ha-ras,Genes, v-Ki-ras,H ras Genes,H ras Oncogenes,H-ras Gene,H-ras Oncogene,Ha ras Genes,Ha ras Oncogenes,Ha-ras Gene,Ha-ras Oncogene,K ras Genes,K ras Oncogenes,K-ras Gene,K-ras Oncogene,Ki ras Genes,Ki ras Oncogenes,Ki-ras Gene,Ki-ras Oncogene,N ras Genes,N ras Oncogenes,N-ras Gene,N-ras Oncogene,c H ras Genes,c H ras Proto Oncogenes,c Ha ras Genes,c Ha ras Proto Oncogenes,c K ras Genes,c K ras Proto Oncogenes,c Ki ras Genes,c Ki ras Proto Oncogenes,c N ras Genes,c N ras Proto Oncogenes,c-H-ras Gene,c-H-ras Proto-Oncogene,c-Ha-ras Gene,c-Ha-ras Proto-Oncogene,c-K-ras Gene,c-K-ras Proto-Oncogene,c-Ki-ras Gene,c-Ki-ras Proto-Oncogene,c-N-ras Gene,c-N-ras Proto-Oncogene,ras Gene,ras Oncogenes,v H ras Genes,v H ras Oncogenes,v Ha ras Genes,v Ha ras Oncogenes,v K ras Genes,v K ras Oncogenes,v Ki ras Genes,v Ki ras Oncogenes,v-H-ras Gene,v-H-ras Oncogene,v-Ha-ras Gene,v-Ha-ras Oncogene,v-K-ras Gene,v-K-ras Oncogene,v-Ki-ras Gene,v-Ki-ras Oncogene
D005260 Female Females

Related Publications

K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene.
January 2002, Toxicologic pathology,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Susceptibility to urethane carcinogenesis of transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) and its modification by butylhydroxytoluene.
October 1999, Cancer letters,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Chemically induced tumors in transgenic mice carrying prototype human c-Ha-ras genes.
January 1991, Princess Takamatsu symposia,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Inhibition by ethinylestradiol of N-ethyl-N-nitrosourea-initiated uterine carcinogenesis in transgenic mice carrying a human prototype C-Ha-ras gene (rasH2 mice).
January 2003, Toxicologic pathology,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Tumor promoting effect of phenolphthalein on development of lung tumors induced by N-ethyl-N-nitrosourea in transgenic mice carrying human prototype c-Ha-ras gene.
June 2002, The Journal of veterinary medical science,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Changes in hepatic enzyme activities in transgenic mice carrying human prototype c-Ha-ras gene treated with diethylnitrosamine.
November 2002, The Journal of veterinary medical science,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Validation of transgenic mice carrying the human prototype c-Ha-ras gene as a bioassay model for rapid carcinogenicity testing.
February 1998, Environmental health perspectives,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Histopathological characterization of the skeletal myopathy in rasH2 mice carrying human prototype c-Ha-ras gene.
May 2005, The Journal of veterinary medical science,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
Glomerulonephritis with fibrillary deposition in a transgenic mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse).
January 2000, Toxicologic pathology,
K Mitsumori, and K Yasuhara, and I Mori, and S Hayashi, and T Shimo, and H Onodera, and T Nomura, and Y Hayashi
[Pulmonary fibrosis in rats induced by N-methyl-N-nitrosourethane].
June 1972, Nihon Kyobu Shikkan Gakkai zasshi,
Copied contents to your clipboard!