Effect of Atm Disruption on Spontaneously Arising and Radiation-Induced Deletion Mutations in Mouse Liver

• Published in: Radiation research 2003-11, Vol.160 (5), p.549-558
• Main Authors: Furuno-Fukushi, Ikuko, Masumura, Ken-ichi, Furuse, Takeshi, Noda, Yuko, Takahagi, Masahiko, Saito, Toshiyuki, Hoki, Yuko, Suzuki, Hiroshi, Wynshaw-Boris, Anthony, Nohmi, Takehiko, Tatsumi, Kouichi
• Format: Article
• Language: English
• Subjects: Animals; Ataxia telangiectasia; Ataxia Telangiectasia - genetics; Ataxia Telangiectasia - metabolism; Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Cell cycle; Cell Cycle Proteins; Cell lines; DNA damage; DNA-Binding Proteins; Dose-Response Relationship, Radiation; Female; Gene Deletion; Gene Expression Regulation - radiation effects; Genetic mutation; Ionizing radiation; Irradiation; Liver; Liver - metabolism; Liver - pathology; Liver - radiation effects; Male; Medical sciences; Mice; Mice, Transgenic; Mutation - radiation effects; Polymerase chain reaction; Protein-Serine-Threonine Kinases - deficiency; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Radiation Dosage; Radiation Tolerance; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); REGULAR ARTICLES; Technology. Biomaterials. Equipments. Material. Instrumentation; Transgenic animals; Tumor Suppressor Proteins
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR3073

Furuno-Fukushi, I., Masumura, K., Furuse, T., Noda, Y., Takahagi, M., Saito, T., Hoki, Y., Suzuki, H., Wynshaw-Boris, A., Nohmi, T. and Tatsumi, K. Effect of Atm Disruption on Spontaneously Arising and Radiation-Induced Deletion Mutations in Mouse Liver. Radiat. Res. 160, 549–558 (2003). Deletion mutations were efficiently recovered in mouse liver after total-body irradiation with X rays by using a transgenic mouse “gpt-delta” system that harbored a lambda EG10 shuttle vector with the red and gam genes for Spi− (sensitive to P2 lysogen interference) selection. We incorporated this system into homozygous Atm-knockout mice as a model of the radiosensitive hereditary disease ataxia telangiectasia (AT). Lambda phages recovered from the livers of X-irradiated mice with the Atm+/+ genotype showed a dose-dependent increase in the Spi− mutant frequency up to sixfold at 50 Gy over the unirradiated control of 2.8 × 10−6. The livers from Atm−/− mice yielded a virtually identical dose–response curve for X rays with a background fraction of 2.4 × 10−6. Structural analyses revealed no significant difference in the proportion of −1 frameshifts and larger deletions between Atm+/+ and Atm−/− mice, although larger deletions prevailed in X-ray-induced Spi− mutants irrespective of Atm status. While a possible defect in DNA repair after irradiation has been strongly indicated in the literature for nondividing cultured cells in vitro from AT patients, the Atm disruption does not significantly affect radiation mutagenesis in the stationary mouse liver in vivo.