Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity. 2020

Vesna Todorovic, and Ajda Prevc, and Martina Niksic Zakelj, and Monika Savarin, and Simon Bucek, and Blaz Groselj, and Primoz Strojan, and Maja Cemazar, and Gregor Sersa
Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia.

Background Management of locoregionally recurrent head and neck squamous cell carcinomas (HNSCC) is challenging due to potential radioresistance. Pulsed low-dose rate (PLDR) irradiation exploits phenomena of increased radiosensitivity, low-dose hyperradiosensitivity (LDHRS), and inverse dose-rate effect. The purpose of this study was to evaluate LDHRS and the effect of PLDR irradiation in isogenic HNSCC cells with different radiosensitivity. Materials and methods Cell survival after different irradiation regimens in isogenic parental FaDu and radioresistant FaDu-RR cells was determined by clonogenic assay; post irradiation cell cycle distribution was studied by flow cytometry; the expression of DNA damage signalling genes was assesed by reverse transcription-quantitative PCR. Results Radioresistant Fadu-RR cells displayed LDHRS and were more sensitive to PLDR irradiation than parental FaDu cells. In both cell lines, cell cycle was arrested in G2/M phase 5 hours after irradiation. It was restored 24 hours after irradiation in parental, but not in the radioresistant cells, which were arrested in G1-phase. DNA damage signalling genes were under-expressed in radioresistant compared to parental cells. Irradiation increased DNA damage signalling gene expression in radioresistant cells, while in parental cells only few genes were under-expressed. Conclusions We demonstrated LDHRS in isogenic radioresistant cells, but not in the parental cells. Survival of LDHRS-positive radioresistant cells after PLDR was significantly reduced. This reduction in cell survival is associated with variations in DNA damage signalling gene expression observed in response to PLDR most likely through different regulation of cell cycle checkpoints.

UI MeSH Term Description Entries
D008938 Mitosis A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D009364 Neoplasm Recurrence, Local The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site. Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D011836 Radiation Tolerance The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS. Radiation Sensitivity,Radiosensitivity,Sensitivity, Radiation,Tolerance, Radiation,Radiation Sensitivities,Radiation Tolerances,Radiosensitivities,Sensitivities, Radiation,Tolerances, Radiation
D011879 Radiotherapy Dosage The total amount of radiation absorbed by tissues as a result of radiotherapy. Dosage, Radiotherapy,Dosages, Radiotherapy,Radiotherapy Dosages
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006258 Head and Neck Neoplasms Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651) Cancer of Head and Neck,Head Cancer,Head Neoplasm,Head and Neck Cancer,Head and Neck Neoplasm,Neck Cancer,Neck Neoplasm,Neck Neoplasms,Neoplasms, Upper Aerodigestive Tract,UADT Neoplasm,Upper Aerodigestive Tract Neoplasm,Upper Aerodigestive Tract Neoplasms,Cancer of Head,Cancer of Neck,Cancer of the Head,Cancer of the Head and Neck,Cancer of the Neck,Head Neoplasms,Head, Neck Neoplasms,Neoplasms, Head,Neoplasms, Head and Neck,Neoplasms, Neck,UADT Neoplasms,Cancer, Head,Cancer, Neck,Cancers, Head,Cancers, Neck,Head Cancers,Neck Cancers,Neoplasm, Head,Neoplasm, Neck,Neoplasm, UADT,Neoplasms, UADT
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077195 Squamous Cell Carcinoma of Head and Neck The most common type of head and neck carcinoma that originates from cells on the surface of the NASAL CAVITY; MOUTH; PARANASAL SINUSES, SALIVARY GLANDS, and LARYNX. Mutations in TNFRSF10B, PTEN, and ING1 genes are associated with this cancer. HNSCC,Head And Neck Squamous Cell Carcinomas,Hypopharyngeal Squamous Cell Carcinoma,Laryngeal Squamous Cell Carcinoma,Oral Cavity Squamous Cell Carcinoma,Oral Squamous Cell Carcinoma,Oral Squamous Cell Carcinomas,Oral Tongue Squamous Cell Carcinoma,Oropharyngeal Squamous Cell Carcinoma,Squamous Cell Carcinoma of Larynx,Squamous Cell Carcinoma of the Larynx,Squamous Cell Carcinoma of the Mouth,Squamous Cell Carcinoma of the Nasal Cavity,Carcinoma, Squamous Cell of Head and Neck,Head and Neck Squamous Cell Carcinoma,Squamous Cell Carcinoma of the Head and Neck,Squamous Cell Carcinoma, Head And Neck

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