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A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia.

Authors
  • Mizumoto, Kazuhiro
  • Qian, Li-Wu
  • Zhang, Li
  • Nagai, Eishi
  • Kura, Shinobu
  • Tanaka, Masao
Type
Published Article
Journal
Journal of radiation research
Publication Date
Mar 01, 2002
Volume
43
Issue
1
Pages
43–51
Identifiers
PMID: 12056329
Source
Medline
License
Unknown

Abstract

The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gamma-ray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluorescence intensity of propidium iodide before and after a digitonin treatment. The sensitizing effect of PR-350 on cell killing by high-dose irradiation was confirmed by time-course, dose-dependency, and microscopic observations. In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry. The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer.

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