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

Abstract

BackgroundManagement 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 methodsCell 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.ResultsRadioresistant 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.ConclusionsWe 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.

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies

“…1a), hyper-radiosensitivity (HRS) is observed in cancer cells exposed to low-dose rate radiotherapy (<0.30 Gy), with a steeper slope of survival curve than that of high-dose rate radiotherapy. When the radiotherapy dose reaches 0.30-0.60 Gy, radiosensitivity begins to shift to increased radioresistance (IRR) (Todorovic et al, 2020). The HRS/IRR phenomenon can be defined using the induced repair model: SF…”

The Effect of High-Dose-Rate Pulsed Radiation on the Survival of Clinically Relevant Radioresistant Cells

“…HRS is generally detected via fluorescence-activated cell sorting and microscopy [30]. Todorovic et al [10] reported that radioresistant cells were more sensitive to PLDR at a unit dose of 0.3 Gy, wherein radioresistant cells showed more HRS than its parental cells. However, they noted that the enhanced cytotoxic effect of PLDR disappeared at lower unit doses (0.2 Gy), and that HRS could not be observed in radioresistant cells.…”

“…On the other hand, the feasibility of using LDFRT as a potentiator of chemotherapy has been studied, and the Life 2021, 11, 1295 2 of 15 results of clinical trials have indicated improved efficacy [8]. In addition, the technique of pulsed low-dose rate radiotherapy (PLDR), which involves irradiation with 0.2 Gy at 3 min intervals for a total of 2 Gy, resulting in an apparent dose rate of 0.0667 Gy/min (total 2 Gy irradiation in 30 min), has been used for the purpose of re-irradiation [9,10]. PLDR [11] was developed as an irradiation method that involves applying HRS and reverses dose rate effects.…”

Biological factors of the tumour response to electrochemotherapy: Review of the evidence and a research roadmap

“…ECT with BLM was equally effective on naïve and radioresistant tumours, whereas radioresistant tumours were more resistant to ECT with CDDP compared with radionaïve tumours [39]. All these outcomes were associated with increased DNA damage repair in resistant tumour cells [40].…”