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Loss of atm radiosensitizes multiple p53 null tissues.

Publication ,  Journal Article
Westphal, CH; Hoyes, KP; Canman, CE; Huang, X; Kastan, MB; Hendry, JH; Leder, P
Published in: Cancer Res
December 15, 1998

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

December 15, 1998

Volume

58

Issue

24

Start / End Page

5637 / 5639

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Time Factors
  • Radiation Tolerance
  • Proteins
  • Protein Serine-Threonine Kinases
  • Oncology & Carcinogenesis
  • Mice, Inbred Strains
  • Mice
  • In Vitro Techniques
  • Heterozygote
 

Citation

APA
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MLA
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Westphal, C. H., Hoyes, K. P., Canman, C. E., Huang, X., Kastan, M. B., Hendry, J. H., & Leder, P. (1998). Loss of atm radiosensitizes multiple p53 null tissues. Cancer Res, 58(24), 5637–5639.
Westphal, C. H., K. P. Hoyes, C. E. Canman, X. Huang, M. B. Kastan, J. H. Hendry, and P. Leder. “Loss of atm radiosensitizes multiple p53 null tissues.Cancer Res 58, no. 24 (December 15, 1998): 5637–39.
Westphal CH, Hoyes KP, Canman CE, Huang X, Kastan MB, Hendry JH, et al. Loss of atm radiosensitizes multiple p53 null tissues. Cancer Res. 1998 Dec 15;58(24):5637–9.
Westphal, C. H., et al. “Loss of atm radiosensitizes multiple p53 null tissues.Cancer Res, vol. 58, no. 24, Dec. 1998, pp. 5637–39.
Westphal CH, Hoyes KP, Canman CE, Huang X, Kastan MB, Hendry JH, Leder P. Loss of atm radiosensitizes multiple p53 null tissues. Cancer Res. 1998 Dec 15;58(24):5637–5639.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

December 15, 1998

Volume

58

Issue

24

Start / End Page

5637 / 5639

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Time Factors
  • Radiation Tolerance
  • Proteins
  • Protein Serine-Threonine Kinases
  • Oncology & Carcinogenesis
  • Mice, Inbred Strains
  • Mice
  • In Vitro Techniques
  • Heterozygote