Abstract | BACKGROUND AND PURPOSE: MATERIALS AND METHODS: In vitro, four established human pancreatic cancer cell lines (SUIT-2, PANC-1, MIA PaCa-2 and BxPC-3) and murine SCCVII tumor cells (for comparison) were used. These cells were treated with 0.4 or 1 mM doranidazole for 45 mm prior to and during aerobic or hypoxic irradiation, and the cell survival was determined using the colony assay. In vivo, Balb/c nude mice bearing the pancreatic cancers (about 200 mg) on their backs received whole-body irradiation either after cervical dislocation, without physical restraint or anesthesia, or 20 min after intravenous injection of 100 mg/kg (0.4 mmol/kg) or 250 mg/kg (1 mmol/kg) of doranidazole. Following irradiation, the in vivo-in vitro assay was performed. The hypoxic fraction was estimated by the paired survival curve method. RESULTS: Regarding in vitro radiosensitivity, there were no characteristics common to the four pancreatic cancer cell lines. In vitro, doranidazole had no sensitizing effect under aerobic conditions, but under hypoxic conditions, its sensitizer enhancement ratio (SER) was 1.25-1.3 at 0. 4 mM and 1.4-1.55 at 1 mM against the four pancreatic cancer cell lines. These SERs were similar to those obtained in SCCVII cells. In vivo, the hypoxic fraction was 20% (95% CI, 11-38%) in SUIT-2, 14% (6.5-28%) in PANC-1, 10% (5.9-16%) in MIA PaCa-2, and 27% (15-46%) in BxPC-3 tumors. The SER of doranidazole was 1.15-1.3 at the dose of 100 mg/kg and 1.35-1.45 at 250 mg/kg. CONCLUSIONS:
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Authors | Y Shibamoto, T Kubota, K Kishii, M Tsujitani |
Journal | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
(Radiother Oncol)
Vol. 56
Issue 2
Pg. 265-70
(Aug 2000)
ISSN: 0167-8140 [Print] Ireland |
PMID | 10927148
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Imidazoles
- Radiation-Sensitizing Agents
- doranidazole
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Topics |
- Animals
- Cell Survival
- Humans
- Imidazoles
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Pancreas
(cytology, drug effects, radiation effects)
- Pancreatic Neoplasms
(drug therapy, radiotherapy)
- Radiation Tolerance
- Radiation-Sensitizing Agents
(pharmacology)
- Reference Values
- Sensitivity and Specificity
- Tumor Cells, Cultured
- Whole-Body Irradiation
(methods)
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