Different mechanisms of cell death in radiosensitive and radioresistant p53 mutated head and neck squamous cell carcinoma cell lines exposed to carbon ions and x-rays.
OBJECTIVE
We initiated studies on the mechanisms of cell death in head and neck squamous cell carcinoma cell lines (HNSCC) since recent clinical trials have shown that local treatment of HNSCC by carbon hadrontherapy is less efficient than it is in other radioresistant cancers.


METHODS
Two p53-mutated HNSCC cell lines displaying opposite radiosensitivity were used. Different types of cell death were determined after exposure to carbon ions (33.6 and 184 keV/microm) or X-rays.


RESULTS
Exposure to radiation with high linear energy transfer (LET) induced clonogenic cell death for SCC61 (radiosensitive) and SQ20B (radioresistant) cells, the latter systematically showing less sensitivity. Activation of an early p53-independent apoptotic process occurred in SCC61 cells after both types of irradiation, which increased with time, dose and LET. In contrast, SQ20B cells underwent G2/M arrest associated with Chk1 activation and Cdc2 phosphorylation. This inhibition was transient after X-rays, compared with a more prolonged and LET-dependent accumulation after carbon irradiation. After release, a LET-dependent increase of polyploid and multinucleated cells, both typical signs of mitotic catastrophe, was identified. However, a subpopulation of SQ20B cells was able to escape mitotic catastrophe and continue to proliferate.


CONCLUSIONS
High LET irradiation induced distinct types of cell death in HNSCC cell lines and showed an increased effectiveness compared with X-rays. However, the reproliferation of SQ20B may explain the potential locoregional recurrence observed among some HNSCC patients treated by hadrontherapy. An adjuvant treatment forcing the tumor cells to enter apoptosis may therefore be necessary to improve the outcome of radiotherapy.
Université Lyon I, Université de Lyon, France.
Mira
M
Maalouf
Gersende
G
Alphonse
Anthony
A
Colliaux
Michaël
M
Beuve
Selena
S
Trajkovic-Bodennec
Priscillia
P
Battiston-Montagne
Isabelle
I
Testard
Olivier
O
Chapet
Marcel
M
Bajard
Gisela
G
Taucher-Scholz
Claudia
C
Fournier
Claire
C
Rodriguez-Lafrasse
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D016195:G2 Phase / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D018499:Linear Energy Transfer; D008938:Mitosis / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism
D002250:Carbon Radioisotopes; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D016203:CDC2 Protein Kinase; D001616:beta-Galactosidase