title: Regulation of DNA damage response and cell cycle in radiation-resistant             HL60 myeloid leukemia cells.
abstract: The acquisition of resistance to radiation has been a matter of concern             in clinical cases. However, mechanisms underlying the acquisition of radiation             resistance are yet to be elucidated. We established a radiation-resistant strain             (Res-HL60 cells) from HL60 leukemic cells and investigated their response to radiation.             Res-HL60 cells not only proliferated on the fifth day after radiation but also             had a high survival rate in a clonogenic assay. Although Chk1 was activated in             HL60 cells after irradiation, the expression levels of Chk1 in Res-HL60 cells             decreased. There were few differences between the two cell lines with regard to             Chk2 activity. Res-HL60 cells show prolonged G2/M arrest and an early decrease             in the extent of DNA damage. However, inhibitors against ATM/ATR and DNA-dependent             protein kinase (DNA-PK) both abrogated the radiation resistance capacity of the             cells. These results reveal that radiation-resistant strains have a high repair             capacity, and inhibition of the repair system at an early stage is an effective             strategy in the second round of radiation therapy.
authors.affiliation: Department of Radiological Life Sciences, Division of Medical                     Life Sciences, Hirosaki University, 66-1 Honcho, Hirosaki, Aomori 036-8564,                     Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hazawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshino
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D002110:Caffeine / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D048430:Cell Shape / Q000528:radiation effects; D048429:Cell Size; D002470:Cell Survival / Q000528:radiation effects; D000071877:Checkpoint Kinase 1; D002867:Chromones / Q000494:pharmacology; D053938:DNA Fragmentation; D004260:DNA Repair / Q000187:drug effects; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression / Q000528:radiation effects; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid; D059566:M Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D009025:Morpholines / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011836:Radiation Tolerance; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C479235:2-(morpholin-4-yl)benzo(h)chromen-4-one; D018797:Cell Cycle Proteins; D002867:Chromones; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D009025:Morpholines; D025521:Tumor Suppressor Proteins; D002110:Caffeine; D011494:Protein Kinases; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3