AffiliationDepartment of Genetics and HHMI, Harvard Medical School, Boston, Massachusetts 02115, USA.
MetadataShow full item record
AbstractAn unusual clinical finding in ataxia-telangiectasia, a human disorder caused by mutations in atm, is exquisite sensitivity to gamma irradiation. By contrast, homozygous deletion of p53 is marked by radiation resistance in certain tissue compartments. Previous studies (A. J. Levine, Cell, 88: 323-331, 1997) have shown that, in vitro, p53-deficient bone marrow cells are resistant to gamma irradiation. Furthermore, the gastrointestinal radiosensitization engendered by the loss of atm has recently been shown (C. H. Westphal et al., Nat. Genet., 16: 397-401, 1997) to be independent of p53. Expanding on previous work, we have looked at in vivo bone marrow resistance in p53-deficient mice. Our results indicate that inbred FVB strain p53 null mice survive lethal irradiation doses because of bone marrow resistance. Moreover, the deletion of atm radiosensitizes even p53 null bone marrow and mouse embryonic fibroblast cells. The results presented here argue that the loss of atm radiosensitizes multiple tissues in a p53-independent manner. Hence, functional inhibition of atm in p53 null and p53 wild-type human tumors may be a useful adjunct to gamma irradiation-based antitumor therapy.
CitationLoss of atm radiosensitizes multiple p53 null tissues. 1998, 58 (24):5637-9 Cancer Res.
- atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity.
- Authors: Westphal CH, Rowan S, Schmaltz C, Elson A, Fisher DE, Leder P
- Issue date: 1997 Aug
- Relationship between DNA double-strand break rejoining and cell survival after exposure to ionizing radiation in human fibroblast strains with differing ATM/p53 status: implications for evaluation of clinical radiosensitivity.
- Authors: Mirzayans R, Severin D, Murray D
- Issue date: 2006 Dec 1
- Genetic interactions between atm and p53 influence cellular proliferation and irradiation-induced cell cycle checkpoints.
- Authors: Westphal CH, Schmaltz C, Rowan S, Elson A, Fisher DE, Leder P
- Issue date: 1997 May 1
- Atm heterozygosity does not increase tumor susceptibility to ionizing radiation alone or in a p53 heterozygous background.
- Authors: Mao JH, Wu D, DelRosario R, Castellanos A, Balmain A, Perez-Losada J
- Issue date: 2008 Nov 20
- Activation of interferon-stimulated genes by gamma-ray irradiation independently of the ataxia telangiectasia mutated-p53 pathway.
- Authors: Sugihara T, Murano H, Nakamura M, Ichinohe K, Tanaka K
- Issue date: 2011 Apr