Effects of chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes

Mutat Res Genet Toxicol Environ Mutagen. 2017 Jan:813:18-26. doi: 10.1016/j.mrgentox.2016.11.005. Epub 2016 Nov 22.

Abstract

Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53+/-) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53+/+) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53+/+ C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.

Keywords: Chronic restraint-induced psychological stress; Fluorescence in situ hybridization (FISH); Mouse restraint model; Total body irradiation.

MeSH terms

  • Animals
  • Chromosome Aberrations*
  • Immobilization*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Spleen / radiation effects*
  • Stress, Physiological*
  • Tumor Suppressor Protein p53 / genetics
  • Whole-Body Irradiation

Substances

  • Tumor Suppressor Protein p53