Loss of atm radiosensitizes multiple p53 null tissues

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: 323-33...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-12, Vol.58 (24), p.5637-5639
Main Authors: WESTPHAL, C. H, HOYES, K. P, CANMAN, C. E, XIN HUANG, KASTAN, M. B, HENDRY, J. H, LEDER, P
Format: Article
Language:English
Subjects:
Animals
Ataxia Telangiectasia Mutated Proteins
Biological and medical sciences
Bone Marrow - radiation effects
Cell Cycle Proteins
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
DNA-Binding Proteins
Fibroblasts - radiation effects
Fundamental and applied biological sciences. Psychology
Gene Deletion
Genes, p53
Heterozygote
In Vitro Techniques
Mice
Mice, Inbred Strains
Molecular and cellular biology
Protein-Serine-Threonine Kinases
Proteins - genetics
Radiation Tolerance
Time Factors
Tumor Suppressor Proteins
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445