Quantification of damage due to low-dose radiation exposure in mice: construction and application of a biodosimetric model using mRNA indicators in circulating white blood cells

J Radiat Res. 2016 Jan;57(1):25-34. doi: 10.1093/jrr/rrv066. Epub 2015 Nov 19.

Abstract

Biodosimetry, the measurement of radiation damage in a biologic sample, is a reliable tool for increasing the accuracy of dose estimation. Although established chromosome analyses are suitable for estimating the absorbed dose after high-dose irradiation, biodosimetric methodology to measure damage following low-dose exposure is underdeveloped. RNA analysis of circulating blood containing radiation-sensitive cells is a candidate biodosimetry method. Here we quantified RNA from a small amount of blood isolated from mice following low-dose body irradiation (<0.5 Gy) aimed at developing biodosimetric tools for situations that are difficult to study in humans. By focusing on radiation-sensitive undifferentiated cells in the blood based on Myc RNA expression, we quantified the relative levels of RNA for DNA damage-induced (DDI) genes, such as Bax, Bbc3 and Cdkn1a. The RNA ratios of DDI genes/Myc in the blood increased in a dose-dependent manner 4 h after whole-body irradiation at doses ranging from 0.1 to 0.5 Gy (air-kerma) of X-rays, regardless of whether the mice were in an active or resting state. The RNA ratios were significantly increased after 0.014 Gy (air-kerma) of single X-ray irradiation. The RNA ratios were directly proportional to the absorbed doses in water ranging from 0.1 to 0.5 Gy, based on gamma-irradiation from (137)Cs. Four hours after continuous irradiation with gamma-rays or by internal contamination with a beta-emitter, the increased RNA ratios resembled those following single irradiation. These findings indicate that the RNA status can be utilized as a biodosimetric tool to estimate low-dose radiation when focusing on undifferentiated cells in blood.

Keywords: Bax; Bbc3; Cdkn1a; Myc; circadian rhythm; cysteamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / radiation effects
  • Animals
  • Circadian Rhythm / radiation effects
  • DNA Damage* / genetics
  • Dose-Response Relationship, Radiation
  • Gamma Rays
  • Leukocytes / metabolism*
  • Leukocytes / radiation effects*
  • Male
  • Mice
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation Exposure*
  • Radiation-Protective Agents / pharmacology
  • Radiometry / methods*
  • X-Rays

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Radiation-Protective Agents