Chromosomal Location of Genes Differentially Expressed in Tumor Cells Surviving High-Dose X-ray Irradiation: A Preliminary Study on Radio-Fragile Sites

Curr Issues Mol Biol. 2021 Sep 8;43(2):1133-1141. doi: 10.3390/cimb43020080.

Abstract

Altered gene expression is a common feature of tumor cells after irradiation. Our previous study showed that this phenomenon is not only an acute response to cytotoxic stress, instead, it was persistently detected in tumor cells that survived 10 Gy irradiation (IR cells). The current understanding is that DNA double-strand breaks (DSBs) are recognized by the phosphorylation of histone H2AX (H2AX) and triggers the ataxia-telangiectasia mutated (ATM) protein or the ATM- and Rad3-related (ATR) pathway, which activate or inactivate the DNA repair or apoptotic or senescence related molecules and causes the expression of genes in many instances. However, because changes in gene expression persist after passaging in IR cells, it may be due to the different pathways from these transient intracellular signaling pathways caused by DSBs. We performed microarray analysis of 30,000 genes in radiation-surviving cells (H1299-IR and MCF7-IR) and found an interesting relation between altered genes and their chromosomal loci. These loci formed a cluster on the chromosome, especially on 1q21 and 6p21-p22 in both irradiated cell lines. These chromosome sites might be regarded as "radio-fragile" sites.

Keywords: X-ray irradiation; chromosome; fragile site; tumor cells.

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Cell Line, Tumor
  • Chromosome Fragile Sites / radiation effects*
  • DNA Repair
  • Genetic Loci / radiation effects
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Phosphorylation
  • Signal Transduction / radiation effects*
  • X-Rays

Substances

  • H2AX protein, human
  • Histones
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins