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J Cancer Metastasis Treat 2016;2 Suppl 1

exposure to cisplatin in vitro. DNA damage was number of γH2AX foci was detected in radiosensitive
evaluated in all cell lines in response to ionizing 2A3 cells (more than 20/nuclei), whereas in FaDu cells
radiation by quantification of H2AX foci. HNSCC cell 11 γH2AX foci/nuclei were detected. In radioresistant
lines used in the experiments were FaDu, a HPV- FaDu-RR cells, only 7 γH2AX foci/nuclei were detected
positive cell line 2A3, derived from FaDu cells, and 30 min after ionizing radiation. The level of γH2AX foci
a radioresistant cell line FaDu-RR, established from 24 h after ionizing radiation was reduced in all cell
FaDu cells by repeated exposure to ionizing radiation. lines, however only in radioresistant FaDu-RR cells the
Radioresistant FaDu-RR cells were recovered after number of residual γH2AX foci was similar to the level
exposure to fractionated ionizing radiation (a total dose of γH2AX foci in unirradiated cells. In FaDu and 2A3
of 120 Gy). cells, the number of residual γH2AX foci was reduced
approximately by half.
The selected HNSCC cell lines responded differently
to ionizing radiation and cisplatin. FaDu-RR cells were A different response to ionizing radiation and exposure
the most radioresistant with a dose modifying factor to cisplatin was observed in tested HNSCC cell lines.
(DMF) at ED 1.66 compared to FaDu cells. Contrary, Namely, repeated exposure to ionizing radiation
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a HPV-positive 2A3 cells were more sensitive to
ionizing radiation than FaDu cells (DMF at ED 0.47). induced radioresistance and resistance to cisplatin in
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In addition, FaDu-RR cells also displayed cross- FaDu-RR cell line, whereas 2A3, a HPV-positive cell
resistance to cisplatin (1.8-fold potentiation in IC line, were more sensitive to ionizing radiation and
50
value) compared to FaDu cells, whereas 2A3 cells cisplatin compared to parental FaDu cell line. The
were more sensitive to cisplatin compared to FaDu observed differences in radiosensitivity of HNSCC cell
cells (2.9-fold reduction in IC value). lines can be at least partly contributed to induction
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and clearance of γH2AX foci after ionizing radiation
DNA damage after ionizing radiation was quantified by indicating differences in DNA damage repair.
detection of H2AX foci, which correlates to DNA double
strand breaks. In all three cell lines, a peak of γH2AX Key words:
foci was detected as early as 30 min after ionizing Radioresistance, head and neck, squamous cell
radiation. Interestingly, at this time point a maximum carcinoma, chemoresistance, cisplatin, H2AX foci

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