title: Radioprotective effect of hypothermia on cells - a multiparametric approach to delineate the mechanisms.
abstract: OBJECTIVE
  Low temperature (hypothermia) during irradiation of cells has been reported to have a radioprotective effect. The mechanisms are not fully understood. This study further investigates the possible mechanisms behind hypothermia-mediated radioprotection.
  
  
  METHODS
  Human lymphoblastoid TK6 cells were incubated for 20 min at 0.8 or 37°C and subsequently exposed to 1 Gy of γ- or X-rays. The influence of ataxia telangiectasia mutated (ATM)-mediated double-strand break signalling and histone deacetylase-dependent chromatin condensation was investigated using the micronucleus assay. Furthermore, the effect of hypothermia was investigated at the level of phosphorylated histone 2AX (γH2AX) foci, clonogenic cell survival and micronuclei in sequentially-harvested cells.
  
  
  RESULTS
  The radioprotective effect of hypothermia (called the temperature effect [TE]) was evident only at the level of micronuclei at a single fixation time, was not influenced by the inhibition of ATM kinase activity and completely abolished by the histone deacetylase inhibition. No TE was seen at the level of γH2AX foci and cell survival.
  
  
  CONCLUSIONS
  We suggest that low temperature during irradiation can induce a temporary cell cycle shift, which could lead to a reduced micronucleus frequency. Future experiments focused on cell cycle progression are needed to confirm this hypothesis.
authors.affiliation: Centre for Radiation Protection Research, GMT Department, Stockholm University, Stockholm, Sweden.
authors.forename: Li
authors.initials: L
authors.lastname: Dang
authors.forename: Halina
authors.initials: H
authors.lastname: Lisowska
authors.forename: Sara Shakeri
authors.initials: SS
authors.lastname: Manesh
authors.forename: Alice
authors.initials: A
authors.lastname: Sollazzo
authors.forename: Marta
authors.initials: M
authors.lastname: Deperas-Kaminska
authors.forename: Elina
authors.initials: E
authors.lastname: Staaf
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
authors.forename: Karl
authors.initials: K
authors.lastname: Brehwens
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wojcik
mesh_terms: D002453:Cell Cycle / Q000502:physiology* / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations / Q000528:radiation effects; D003080:Cold Temperature; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D008214:Lymphocytes / Q000502:physiology* / Q000528:radiation effects*; D008954:Models, Biological; D011835:Radiation Protection / Q000379:methods*; D011836:Radiation Tolerance / Q000502:physiology*