Journal article
Mitochondrial DNA Depletion Induces Radioresistance by Suppressing G2 Checkpoint Activation in Human Pancreatic Cancer Cells
Radiation research, Vol.171(5), pp.581-587
05/2009
DOI: 10.1667/RR1395.1
PMCID: PMC2707769
PMID: 19580493
Abstract
We hypothesized that mitochondrial function regulates cell cycle checkpoint activation and radiosensitivity. Human pancreatic tumor cells (MiaPaCa-2, rho
+
) were depleted of mitochondrial DNA (rho°) by culturing cells in the presence of ethidium bromide. Depletion of mitochondrial DNA was verified by PCR amplification of total DNA using primer pairs specific for mitochondrial DNA. Loss of mitochondrial DNA decreased plating efficiency and the percentage of cells in S phase. Exponential cultures were irradiated with 2, 4 and 6 Gy (dose rate: 0.83 Gy/min) of ionizing radiation and harvested for determination of cell viability, growth and cell cycle phase distributions. Rho° cells were radioresistant compared to rho
+
cells, with a dose-modifying factor (DMF) of 1.6. Although cell growth was significantly inhibited in irradiated rho
+
cells compared to unirradiated control cells, the inhibition in Rho° cells was minimal. In addition, mitochondrial DNA depletion suppressed radiation-induced G
2
checkpoint activation, which was accompanied by increases in both cyclin B1 and CDK1. These results suggest that mitochondrial function may regulate cell cycle checkpoint activation and radio-sensitivity in pancreatic cancer cells.
Details
- Title: Subtitle
- Mitochondrial DNA Depletion Induces Radioresistance by Suppressing G2 Checkpoint Activation in Human Pancreatic Cancer Cells
- Creators
- Carla R Cloos - University of Iowa College of Medicine, Iowa City, IowaDavid H Daniels - University of Iowa College of Medicine, Iowa City, IowaAmanda Kalen - Department of Radiation Oncology, Iowa City, IowaKatee Matthews - University of Iowa College of Medicine, Iowa City, IowaJuan Du - Department of Surgery, Iowa City, IowaPrabhat C Goswami - Department of Radiation Oncology, Iowa City, IowaJoseph J Cullen - Department of Surgery, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Radiation research, Vol.171(5), pp.581-587
- DOI
- 10.1667/RR1395.1
- PMID
- 19580493
- PMCID
- PMC2707769
- NLM abbreviation
- Radiat Res
- ISSN
- 0033-7587
- eISSN
- 1938-5404
- Publisher
- Radiation Research Society
- Language
- English
- Date published
- 05/2009
- Academic Unit
- Surgery; Family and Community Medicine; Radiation Oncology
- Record Identifier
- 9984046904302771
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