2.50
Hdl Handle:
http://hdl.handle.net/10541/93086
Title:
Loss of atm radiosensitizes multiple p53 null tissues.
Authors:
Westphal, C H; Hoyes, Katherine P; Canman, C E; Huang, X; Kastan, M B; Hendry, Jolyon H; Leder, P
Abstract:
An 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.
Affiliation:
Department of Genetics and HHMI, Harvard Medical School, Boston, Massachusetts 02115, USA.
Citation:
Loss of atm radiosensitizes multiple p53 null tissues. 1998, 58 (24):5637-9 Cancer Res.
Journal:
Cancer Research
Issue Date:
15-Dec-1998
URI:
http://hdl.handle.net/10541/93086
PubMed ID:
9865712
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWestphal, C Hen
dc.contributor.authorHoyes, Katherine Pen
dc.contributor.authorCanman, C Een
dc.contributor.authorHuang, Xen
dc.contributor.authorKastan, M Ben
dc.contributor.authorHendry, Jolyon Hen
dc.contributor.authorLeder, Pen
dc.date.accessioned2010-02-25T15:55:10Z-
dc.date.available2010-02-25T15:55:10Z-
dc.date.issued1998-12-15-
dc.identifier.citationLoss of atm radiosensitizes multiple p53 null tissues. 1998, 58 (24):5637-9 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid9865712-
dc.identifier.urihttp://hdl.handle.net/10541/93086-
dc.description.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.en
dc.language.isoenen
dc.subjectTumour Suppressor Proteinsen
dc.subject.meshAnimals-
dc.subject.meshBone Marrow-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFibroblasts-
dc.subject.meshGene Deletion-
dc.subject.meshGenes, p53-
dc.subject.meshHeterozygote-
dc.subject.meshMice-
dc.subject.meshMice, Inbred Strains-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshProteins-
dc.subject.meshRadiation Tolerance-
dc.subject.meshTime Factors-
dc.subject.meshTumor Suppressor Proteins-
dc.titleLoss of atm radiosensitizes multiple p53 null tissues.en
dc.typeArticleen
dc.contributor.departmentDepartment of Genetics and HHMI, Harvard Medical School, Boston, Massachusetts 02115, USA.en
dc.identifier.journalCancer Researchen
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