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Radiosensitizing effects of gemcitabine on aerobic and chronically hypoxic HeLa and MRC5 cells in-vitro
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E. Heshmati   , H. Mozdarani , P. Abdolmaleki , K. Khoshaman |
| , mozdarah@modares.ac.ir |
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Abstract: (9548 Views) |
| Background: Gemcitabine (2′, 2′-difluoro-2′-
deoxycytidine, an analogue of deoxycytidine) is a
relatively new drug with wide range of anti-cancer
activity. In this study, radiosensitizing effects of
gemcitabine was investigated on HeLa and MRC5
human originated cell lines under both chronically
hypoxic and normoxic conditions using the
micronucleus (MN) assay. Materials and Methods:
For induction of chronic hypoxia, the cell culture
flasks were saturated with N2 gas. To evaluate the
radiosensitizing effects, in the presence of the
non-genotoxic concentration (1ng/ml) of gemcitabine,
cells were exposed to different doses (0.5, 1, 2 Gy) of
X-ray in both chronically hypoxic and normoxic
conditions. Results: Results showed that there was
no significant difference in MN induction under
chronically hypoxic and normoxic condition when
using 1 ng/ml gemcitabine alone, however in the
absence of drug, MN induction was significantly
different in irradiated cells (P<0.01). Radiosensitizing
effects of gemcitabine in chronic hypoxic condition
was greater than normoxic condition in both cell lines
(P<0.01), although more pronounced in HeLa cells.
Conclusions: Radiosensitizing effects and greater
dose modifying factor of gemcitabine under depleted
oxygen condition is not clearly understood. It might be
due to depletion of deoxynocleotides pools via
inhibition of ribonucleotide reductase and
mismatched nucleosides incorporation into DNA after
radiation exposure. Iran. J. Radiat. Res., 2012 10(1):
11-18
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| Keywords: Gemcitabine, radiosensitizer, hypoxia, HeLa and MRC5 cells, cytochalasin blocked micronucleus assay |
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Full-Text [PDF 385 kb]
(2720 Downloads)
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Type of Study: Original Research |
Subject:
Radiation Biology
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