title: Role of p53 gene in apoptotic repair of genotoxic tissue damage in mice.
abstract: When DNA is damaged by exposure to a small amount of radiation, it is repaired efficiently by innate mechanisms. However, if cellular damage is more extensive, DNA repair cannot be adequately completed. To clarify the role of the p53 gene in apoptotic tissue repair, the incidence of in-vivo radiation-induced somatic mutation was evaluated by measuring the T cell receptor (TCR) gene expression in p53(+/+) and p53(-/-) mice. After gamma-irradiation with 3 Gy, the TCR mutation frequency (MF) was higher in p53(+/+) mice than in the controls. However, when the mice were exposed to 3 Gy at a low dose rate, the TCR MF did not increase in the p53(+/+) mice, whereas it increased and remained elevated in p53(-/-) mice, which are unable to induce apoptosis. In p53(+/+) mice, the TCR MF peaked 9 days after gamma-irradiation with 3 Gy at a high dose rate, and then gradually decreased with a half-life of about 13 days. However, in p53(-/-) mice, the peak level of the TCR MF did not decline significantly with time. Hence, complete repair of mutagenic damage in irradiated tissues requires the integration of DNA repair and p53-dependent apoptotic tissue repair.
authors.affiliation: Department of Radiation Biology & Health, School of Medicine, University of Occupational & Environmental Health, Yahatanishi-ku, Kitakyushu 807-8555, Japan. fumiok@med.uoeh-u.ac.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Kato
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Kakihara
authors.forename: Naoki
authors.initials: N
authors.lastname: Kunugita
authors.forename: Akira
authors.initials: A
authors.lastname: Ootsuyama
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Norimura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D005720:Gamma Rays; D005787:Gene Frequency; D019672:Genes, T-Cell Receptor / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA