Hypothermia modulates the DNA damage response to ionizing radiation in human peripheral blood lymphocytes

Abstract

Purpose: Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage. It was suggested to be due to an effective transformation of DNA damage to chromosomal damage at low temperature. The purpose of the study was to analyze the kinetics of aberration formation during the first hours after exposing human peripheral blood lymphocytes to ionizing radiation at 0.8 °C and 37 °C.

Materials and methods: To this end, we applied the technique of premature chromosome condensation. In addition, DNA damage response was analyzed by measuring the levels of phosphorylated DNA damage responsive proteins ATM, DNA-PK and p53 and mRNA levels of the radiation-responsive genes BBC3, FDXR, GADD45A, XPC, MDM2 and CDKN1A.

Results: A consistently lower frequency of chromosomal breaks was observed in cells exposed at 0.8 °C as compared to 37 °C already after 30 minutes postexposure. This effect was accompanied by elevated levels of phosphorylated ATM and DNA-PK proteins and a reduced immediate level of phosphorylated p53 and of the responsive genes.

Conclusions: Low temperature at exposure appears to promote DNA repair leading to reduced transformation of DNA damage to chromosomal aberrations.

Keywords:

• Hypothermia
• temperature
• premature chromosome condensation
• chromosome aberrations
• DNA damage response

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

The study was partly supported by the Swedish Radiation Safety Authority SSM.

Notes on contributors

Halina Lisowska

Halina Lisowska is a researcher in the field of radiation biology at the Jan Kochanowski University in Kielce. Lisowska focuses on factors influencing the in vitro sensitivity of cells to ionizing radiation.

Lei Cheng

Lei Cheng is a PhD student in the field of radiation biology at the Stockholm University. Cheng focuses on studying gene expression and high resolution electron images of cells exposed to a combination of radiations of different qualities.

Alice Sollazzo

Alice Sollazzo is a PhD student in the field of radiation biology at the Stockholm University. Sollazzo focuses on studying the cellular effects of combined exposure to radiations of different qualities with special reference to live imaging of IRIF formation and decay.

Lovisa Lundholm

Lovisa Lundholm is a researcher in the field of radiation biology at the Stockholm University. Lundholm focuses on the impact of chromatin condensation on the response of cells to radiations of different qualities.

Aneta Wegierek-Ciuk

Aneta Wegierek-Ciuk is a researcher in field of radiation biology/toxicology at the Jan Kochanowski University in Kielce. Wegierek-Ciuk focuses on the genotoxic effects of nanoparticles and on markers of individual radiosensitivity.

Sylwester Sommer

Sylwester Sommer is a researcher in field of radiation biology at the Institute of Nuclear Chemistry and Technology in Warszawa. Sommer main research focus is in development and validation of cytogenetic assays for retrospective biological dosimetry.

Anna Lankoff

Anna Lankoff is a Professor of biology/toxicology at the Jan Kochanowski University in Kielce. Lankoff focuses on the genotoxic effects of nanoparticles and on alpha emitters used in nuclear medicine.

Andrzej Wojcik

Andrzej Wojcik is a Professor of radiation biology at the Stockholm University. Wojcik focuses on studying the cellular effects of combined exposure to radiations of different qualities, with special reference to cytogenetic effects of radiation.