Suitability of scoring PCC rings and fragments for dose assessment after high-dose exposures to ionizing radiation

Mutat Res. 2013 Sep 18;757(1):1-7. doi: 10.1016/j.mrgentox.2013.03.013. Epub 2013 Jul 19.

Abstract

Assessment of radiation doses through measurement of dicentric chromosomes may be difficult due to the inability of damaged cells to reach mitosis. After high-dose exposures, premature chromosome condensation (PCC) has become an important method in biodosimetry. PCC can be induced upon fusion with mitotic cells, or by treatment with chemicals such as calyculin A or okadaic acid. Several different cytogenetic endpoints have been measured with chemically induced PCC, e.g., via scoring of extra chromosome pieces or ring chromosomes. The dose-effect curves published with chemically induced PCC show differences in their coefficients and in the distribution of rings among cells. Here we present a study with calyculin A to induce PCC in peripheral blood lymphocytes irradiated at nine different doses of γ-rays up to 20Gy. Colcemid was also added in order to observe metaphase cells. During microscopical analysis the chromosome aberrations observed in the different cell-cycle phases (G2/M-PCC, M/A-PCC and M cells) were recorded. The proportion of G2/M-PCC cells was predominant from 3 to 20Gy, M cells decreased above 1Gy and M/A-PCC cells remained constant at all doses and showed the highest frequencies of PCC rings. Depending on the cell-cycle phase there was a difference in the linear coefficients in the dose-effect curves of extra fragments and rings. Poisson distribution among PCC rings was observed after calyculin A+colcemid treatment, facilitating the use of this methodology also for partial body exposures to high doses. This has been tested with two simulated partial exposures to 6 and 12Gy. The estimated doses in the irradiated fraction were very close to the real dose, indicating the usefulness of this methodology.

Keywords: Biological dosimetry; Chromosome aberrations; High doses; Ionizing radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chromosome Aberrations* / drug effects
  • Chromosome Aberrations* / radiation effects
  • Chromosomes / drug effects
  • Chromosomes / genetics
  • Chromosomes / radiation effects*
  • Dose-Response Relationship, Radiation
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / radiation effects
  • Marine Toxins
  • Metaphase / drug effects
  • Metaphase / radiation effects
  • Mitosis / radiation effects*
  • Oxazoles / pharmacology
  • Radiation Dosage*
  • Radiation, Ionizing*
  • Ring Chromosomes

Substances

  • Marine Toxins
  • Oxazoles
  • calyculin A