Radiobiological Effects of Low-Dose Radiation in Normal Fibroblasts of Patients with Head and Neck Cancer Treated with Induction Chemotherapy Combined with Low-Dose Fractionated Radiation

TL;DR

This study examines how low-dose radiation affects normal fibroblasts in head and neck cancer patients, finding that individual radiosensitivity plays a bigger role than hyper-radiosensitivity.

Contribution

The study identifies that hyper-radiosensitivity is rare in normal fibroblasts of HNSCC patients and has minimal impact on radiation responses.

Findings

Hyper-radiosensitivity (HRS) was observed in only 15% of HNSCC patient fibroblasts.

Residual DNA damage was higher after fractionated low-dose radiation compared to a single dose.

Chemopotentiating effects of low-dose radiation were not influenced by HRS status.

Abstract

The aim of the study was to define radiobiological effects of single and fractionated low doses in normal fibroblasts in 40 patients with squamous cell carcinoma of the head and neck (HNSCC) treated with induction chemotherapy combined with low-dose fractionated radiation (LDFR) and to answer the question regarding the role of low-dose hyper-radiosensitivity (HRS) in these effects. HRS status was determined using flow cytometry-based clonogenic survival assay (cells were irradiated with doses 0.1–4 Gy of 6 MV X-rays). Radiobiological effects (cell kill, kinetics of DSB recognition and repair, chemopotentiation) of LDFR 4x0.5 Gy and a single dose of 2, 0.5 and 0.2 Gy were estimated by clonogenic, pATM and γH2AX foci assays. HRS response was demonstrated for normal fibroblasts in 6 of the 40 HNSCC patients. For all assessed biological parameters, significant interindividual differences were observed. The presence of HRS had no effect on the chemopotentiating effects of LDFR 4x0.5 Gy, which were similar to that after 2 Gy. There was also no association between HRS and the maximum number of pATM and γH2AX foci induced by single (0.2, 0.5, 2 Gy) or fractionated low doses 4x0.5 Gy. Significantly higher percentages of residual pATM and γH2AX foci observed after LDFR 4x0.5 Gy than after 2 Gy were independent of HRS. HRS is a rare finding (15%) in normal fibroblasts from HNSCC patients; therefore, it is of rather little importance in healthy late-reacting connective tissues. Moreover, the fibroblast response to single and fractionated low doses (alone or in combination with carboplatin and paclitaxel) appeared more dependent on individual radiosensitivity than on HRS.

Figures