No benefits of ultrafractionation in two head-and-neck cancer cell lines with different inherent radiosensitivity.
OBJECTIVE
To assess if ultrafractionation is applicable in the context of an unknown hyperradiosensitivity (HRS) status, we studied the survival and repair capacity of two tumor cell lines after irradiation with two different dose/fractionation schedules that can be used in a clinical setting.


METHODS
Squamous cell carcinoma cell lines SCC-3 (radioresistant) and SCC-6 (radiosensitive) were used. Survival was studied by clonogenic assay after multiple fractions of 0.5 Gy (2 fractions/day, 6-h interval) and 2 Gy (1 fraction/day) for a total dose of 8 Gy of gamma-rays. The capacity to repair single-strand and double-strand breaks (SSB, DSB) was assessed by comet assay. The messenger RNA (mRNA) levels of DNA-dependent protein kinase (PK) components were analyzed by RNase protection and real-time polymerase chain reaction (PCR).


RESULTS
In both cell lines, no apparent difference was noted between the two fractionation protocols. In particular for SCC-3, the mean surviving fraction tended to be lower after 2 Gy than after 0.5 Gy fractions. In SCC-3 and SCC-6 no significant difference was observed in the repair capacity of SSB and DSB after exposure to single doses of 0.5 Gy or 2 Gy. After exposure to the same single doses, the mRNA levels of DNA-PK catalytic subunit (PKcs), Ku 70, and Ku 80 were similar.


CONCLUSIONS
Our data do not support the concept of ultrafractionation, at least when using fractions of 0.5 Gy in the cell lines studied. This suggests that methods for testing HRS status in individual tumors need to be developed before the relevance of ultrafractionation can be investigated in the clinic.
Boehringer-Wyss
Nicole
N
Department of Genetics and Microbiology, University Medical Centre, Geneva, Switzerland. Nicole.Boehringer@medecine.unige.ch
Clarkson
Stuart G
SG
Allal
Abdelkarim S
AS
D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects*; D020552:Comet Assay; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D019583:Dose Fractionation, Radiation; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases