Dependency of repair of radiation-induced damage on p53 status and efficient inhibition of the repair with wortmannin treatment in vivo, with reference to the effect on intratumor quiescent cell population

  • Authors:
    • Shin-Ichiro Masunaga
    • Akihisa Takahashi
    • Ken Ohnishi
    • Kenji Nagata
    • Minoru Suzuki
    • Genro Kashino
    • Yuko Kinashi
    • Takeo Ohnishi
    • Koji Ono
  • View Affiliations

  • Published online on: December 1, 2007     https://doi.org/10.3892/or.18.6.1589
  • Pages: 1589-1596
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Abstract

To examine the dependency of p53 status and the effect of wortmannin on the repair of radiation-induced damage, referring to the response of intratumor quiescent (Q) cells. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into left hind legs of nude mice. Tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received high dose-rate γ-ray irradiation (HDRI) immediately followed by caffeine or wortmannin administration, or reduced dose-rate γ-ray irradiation simultaneously with caffeine or wortmannin administration. Nine hours after the start of irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. SAS/neo tumor cells, especially intratumor Q cell populations, showed a marked reduction in sensitivity due to the repair of radiation-induced damage, compared with the total or Q cell populations within SAS/mp53 tumors that showed little repair capacity. In both total and Q cell populations within SAS/neo tumors, wortmannin efficiently suppressed the reduction in sensitivity caused by leaving an interval between HDRI and the assay and decreasing the irradiation dose rate. The repair of radiation-induced damage was thought to be a p53-dependent event. From the viewpoint of tumor control, including intratumor Q-cell control, wortmannin treatment in combination with γ-ray irradiation is thought to be useful for suppressing the repair of radiation-induced damage.

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December 2007
Volume 18 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Masunaga S, Takahashi A, Ohnishi K, Nagata K, Suzuki M, Kashino G, Kinashi Y, Ohnishi T and Ono K: Dependency of repair of radiation-induced damage on p53 status and efficient inhibition of the repair with wortmannin treatment in vivo, with reference to the effect on intratumor quiescent cell population. Oncol Rep 18: 1589-1596, 2007
APA
Masunaga, S., Takahashi, A., Ohnishi, K., Nagata, K., Suzuki, M., Kashino, G. ... Ono, K. (2007). Dependency of repair of radiation-induced damage on p53 status and efficient inhibition of the repair with wortmannin treatment in vivo, with reference to the effect on intratumor quiescent cell population. Oncology Reports, 18, 1589-1596. https://doi.org/10.3892/or.18.6.1589
MLA
Masunaga, S., Takahashi, A., Ohnishi, K., Nagata, K., Suzuki, M., Kashino, G., Kinashi, Y., Ohnishi, T., Ono, K."Dependency of repair of radiation-induced damage on p53 status and efficient inhibition of the repair with wortmannin treatment in vivo, with reference to the effect on intratumor quiescent cell population". Oncology Reports 18.6 (2007): 1589-1596.
Chicago
Masunaga, S., Takahashi, A., Ohnishi, K., Nagata, K., Suzuki, M., Kashino, G., Kinashi, Y., Ohnishi, T., Ono, K."Dependency of repair of radiation-induced damage on p53 status and efficient inhibition of the repair with wortmannin treatment in vivo, with reference to the effect on intratumor quiescent cell population". Oncology Reports 18, no. 6 (2007): 1589-1596. https://doi.org/10.3892/or.18.6.1589