Reference - Detail
|Author||Hazawa M, Hosokawa Y, Monzen S, Yoshino H, Kashiwakura I.|
|Title||Regulation of DNA damage response and cell cycle in radiation-resistant HL60 myeloid leukemia cells.|
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.
|MeSH||Ataxia Telangiectasia Mutated Proteins Caffeine / pharmacology Caspase 3 / metabolism Cell Cycle Proteins / antagonists & inhibitors Cell Cycle Proteins / metabolism Cell Shape / radiation effects Cell Size Cell Survival / radiation effects Checkpoint Kinase 1 Chromones / pharmacology DNA Fragmentation* DNA Repair / drug effects DNA-Activated Protein Kinase / antagonists & inhibitors DNA-Activated Protein Kinase / metabolism DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / metabolism Gene Expression / radiation effects HL-60 Cells Histones / metabolism Humans Leukemia, Myeloid M Phase Cell Cycle Checkpoints / radiation effects* Morpholines / pharmacology Protein Kinases / genetics Protein Kinases / metabolism Protein-Serine-Threonine Kinases / antagonists & inhibitors Protein-Serine-Threonine Kinases / metabolism Radiation Tolerance* Tumor Suppressor Proteins / antagonists & inhibitors Tumor Suppressor Proteins / metabolism|
|Human and Animal Cells|