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Establishment of Ku70-Deficient Lung Epithelial Cell Lines and Their Hypersensitivity to Low-Dose X-Irradiation.
MedLine Citation:
PMID:  21160137     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In clinical situations, cellular resistance to chemotherapy and radiotherapy is a significant component of tumor treatment failure. The DNA repair protein Ku70 is a key contributor to chemoresistance to anticancer agents, e.g., etoposide and bleomycin, or radioresistance. Ku70 plays a key role as a sensor of DNA double-strand breaks (DSBs) induced following exposure to ionizing radiation as well as treatment with some chemotherapeutic drugs. The responses of different organs to radiation vary widely and likely depend on the cell population in the organs. However, it is not clear whether Ku70 plays a role in the low-dose radioresistance of lung epithelial cells. In this study, we established Ku70-deficient epithelial cell lines from the murine lungs lacking Ku70. Ku70-/- lung epithelial cells exhibited a reduced Ku80 expression. Moreover, Ku70-/- lung epithelial cells were more sensitive than controls (Ku70+/- lung epithelial cells) to low-dose X-irradiation (<0.5 Gy). We also found that consistent with the Ku70 function as a sensor of DSBs, Ku70 mainly localized in the nuclei of murine lung epithelial cells. These findings clearly indicate that Ku70 plays a key role in the regulation of the Ku80 expression level in and the radioresistance of lung epithelial cells. Our data also suggest that these cell lines might be useful not only for the study of Ku70 functions and the DSB repair pathway, but also for the study of the molecular mechanism underlying the sensitivity to chemotherapeutic drugs and radiation in lung epithelial cells.
Authors:
Manabu Koike; Yasutomo Yutoku; Aki Koike
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-13
Journal Detail:
Title:  The Journal of veterinary medical science / the Japanese Society of Veterinary Science     Volume:  -     ISSN:  0916-7250     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9105360     Medline TA:  J Vet Med Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
DNA Repair Gene Res., National Institute of Radiological Sciences.
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