Regulation of XPA could play a role in inhibition of radiation-induced bystander effects in QU-DB cells at high doses

J Cancer Res Ther. 2020 Dec;16(Supplement):S68-S73. doi: 10.4103/jcrt.JCRT_503_18.

Abstract

Introduction: Radiation-induced bystander effects (RIBE) is the radiobiological effects detected in nonirradiated cells that have received signals from neighboring irradiated cells. In some studies, there are observations that RIBE unexpectedly reduces at high doses. In this study, the expression of two selected apoptotic and repair genes and their possible role in the formation of this unexpected reduction is examined.

Materials and methods: The QU-DB cells were irradiated with gamma rays of a60 Co teletherapy unit at doses of 2, 4, 6, and 8 Gy. One hour following irradiation, their culture media were transferred to bystander cells to induced RIBE. After 24 h incubation, the RNA of cells was isolated and cDNA synthesized. Expression levels of BAX, XPA, and XPA/BAX ratio were examined by relative quantitative reverse transcription-polymerase chain reaction.

Results: In target cells, up-regulation of both genes was observed at all doses. In bystander cells, at the low dose (2 Gy), the expression of BAX was more than XPA; at 4 Gy, the ratio was balanced. A significant correlation was found between the XPA/BAX ratio and the dose, at high doses pattern of gene expression dominated by DNA repair gene.

Conclusion: Gene expression profile was distinctive in bystander cells compared to target cells. The observed linear increasing of the ratio of XPA/BAX could support the hypothesis that the DNA repair system is stimulated and causes a reduction in RIBE at high doses.

Keywords: Bystander effects; DNA repair; gene expression; ionizing radiation; lung carcinoma.

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Bystander Effect / genetics
  • Bystander Effect / radiation effects*
  • Cell Line, Tumor
  • DNA Repair / genetics
  • DNA Repair / radiation effects
  • Dose-Response Relationship, Radiation
  • Gene Expression Profiling
  • Gene Expression Regulation / radiation effects*
  • Humans
  • Xeroderma Pigmentosum Group A Protein / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • XPA protein, human
  • Xeroderma Pigmentosum Group A Protein
  • bcl-2-Associated X Protein