Abstract
BackgroundTo evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy.MethodsIn vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days. Flow cytometry was used to assess the expression of γ-H2AX in PBLs. OM was assessed using the World Health Organization (WHO) scores twice a week and correlated with the expression of γ-H2AX.ResultsThe in vitro assay results showed that patients with severe OM had higher γ-H2AX-specific relative fluorescence at various irradiation doses in the damage kinetics assay, with significantly higher γ-H2AX expression at 8 Gy (p = 0.039), and also at 24 hours after irradiation at a dose of 2 Gy in the repair kinetics assay, compared to the patients with mild OM (p = 0.008). The optimal cutoff value for relative fluorescence of γ-H2AX was 0.960, 24 hours post-irradiation. However, there were no significant differences in γ-H2AX expression at different times between the two groups, as assessed with the in vivo assay.ConclusionsThese results suggest that the damage and repair kinetics of γ-H2AX from PBLs in the in vitro study may have predictive value for identifying the grades of OM among HNC patients prior to radiotherapy.
Highlights
To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy
Assessment of damage kinetics using γ-H2AX expression analysis in vitro After irradiation of PBLs, the fluorescence of γ-H2AX increased with the irradiation dose (Figure 1)
There was a strong linear correlation between the relative fluorescence of γ-H2AX in PBLs and the irradiation dose in the patients with severe (r = 0.998; p = 0.000) and mild (r = 0.976; p = 0.005) OM
Summary
To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy. The extent of radiation-induced DNA damage and its repair have been considered to be the most relevant indicators of irradiation-associated toxicity to normal tissue [7]. The correlation of γ-H2AX with DNA damage in peripheral blood lymphocytes (PBLs), blood mononuclear cells, skin, or other human tissues has been observed [10]. A study by Rube et al [13] indicated that γ-H2AX of lymphocytes from children with solid tumors could be used to identify DSB-repair deficiencies in patients who developed severe toxicities to normal tissue after chemo/radiotherapy. No correlation was found by Werbrouck et al [15] between the kinetics of the appearance of γ-H2AX foci and the severity of acute normal tissue reactions
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
