Loss of atm radiosensitizes multiple p53 null tissues.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Westphal, CH; Hoyes, KP; Canman, CE; Huang, X; Kastan, MB; Hendry, JH; Leder, P

Published Date

  • December 15, 1998

Published In

Volume / Issue

  • 58 / 24

Start / End Page

  • 5637 - 5639

PubMed ID

  • 9865712

Pubmed Central ID

  • 9865712

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng

Conference Location

  • United States