Reoxygenation in the SCCVII tumor after KU-2285 sensitization plus single or fractionated irradiation.

Because reoxygenation of solid tumors after irradiation with a hypoxic cell sensitizer has never previously been investigated, we assessed the reoxygenation in SCCVII tumors after treatment with KU-2285 plus single or fractionated irradiation.
KU-2285 (100 mg/kg) was injected intraperitoneally into C3H mice bearing 1-cm SCCVII tumors at 30 min before a single dose of 12 Gy or three fractions of 5 Gy at 12 h intervals. Changes of the hypoxic fraction (HF) were then evaluated by the paired survival curve method.
Since the radiosensitizing effect of KU-2285 was relatively persistent, the HF was only evaluable after 6 h of irradiation. The HF of untreated SCCVII tumors was 9.1%. After treatment with KU-2285 and 12 Gy, the HF was 25% at 6 h, 32% at 12 h, 24% at 24 h, and 7.6% at 72 h. The HF was lower at 6 h than that after radiation alone, but was similar at later periods. After three fractions of 5 Gy with or without KU-2285, the HF was 33% at 6 h in both groups, while it was 12% and 13% at 24 h for tumors pretreated with KU-2285 and those receiving radiation alone, respectively. However, a sensitizing effect of KU-2285 was indicated by the downward shift of the survival curves for tumors irradiated after exposure to this agent.
Reoxygenation occurred quite efficiently in tumors receiving KU-2285 and 12 Gy. After fractionated irradiation, however, reoxygenation was similar in the KU-2285-pretreatment and irradiation alone groups.
AuthorsY Shibamoto, Y Kitakabu, R Murata, N Oya, T Shibata, K Sasai, M Takahashi, M Abe
JournalInternational journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 29 Issue 3 Pg. 583-6 (Jun 15 1994) ISSN: 0360-3016 [Print] UNITED STATES
PMID8005819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • KU 2285
  • Oxygen
  • Animals
  • Carcinoma, Squamous Cell (metabolism)
  • Cell Hypoxia
  • Cell Survival (drug effects, radiation effects)
  • Mice
  • Mice, Inbred C3H
  • Nitroimidazoles (pharmacology)
  • Oxygen (metabolism)
  • Radiation-Sensitizing Agents (pharmacology)

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