Document Detail

Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: impact of DNA repair.
MedLine Citation:
PMID:  18661370     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To ask whether highly metastatic sublines show more marked low-dose hyper-radiosensitivity (HRS) response than poorly metastatic ones. MATERIALS AND METHODS: The progressive (PRO) subline showing tumourigenicity and metastatic potential and the regressive (REG) subline showing neither tumourigenicity nor metastatic potential were both isolated from a parental rat colon tumour. Clonogenic survival, micronuclei and apoptosis, cell cycle distribution, DNA single- (SSB) and double-strand breaks (DSB) induction and repair were examined. RESULTS: HRS phenomenon was demonstrated in PRO subline. Before irradiation, PRO cells show more spontaneous damage than REG cells. After 0.1 Gy, PRO cells displayed: (i) More DNA SSB 15 min post-irradiation, (ii) more unrepaired DNA DSB processed by the non-homologous end-joining (NHEJ) and by the RAD51-dependent recombination pathways, (iii) more micronuclei, than REG cells while neither apoptosis nor p53 phosphorylation nor cell cycle arrest was observed in both sublines. CONCLUSIONS: HRS response of PRO subline may be induced by impairments in NHEJ repair that targets G(1) cells and RAD51-dependent repair that targets S-G(2)/M cells. The cellular consequences of such impairments are a failure to arrest in cell cycle, the propagation of damage through cell cycle, mitotic death but not p53-dependent apoptosis. Tumourigenic cells with high metastatic potential may preferentially show HRS response.
Charles Thomas; Josiane Charrier; Catherine Massart; Michel Cherel; Bernard Fertil; Jacques Barbet; Nicolas Foray
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  84     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  533-48     Citation Subset:  IM; S    
Institut National de la Sante et de la Recherche Medicale (INSERM), U601, Nantes, France.
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MeSH Terms
Apoptosis / radiation effects*
Cell Cycle / radiation effects*
Cell Line, Tumor
Colonic Neoplasms / pathology*
DNA Breaks, Double-Stranded / radiation effects*
DNA Breaks, Single-Stranded / radiation effects*
DNA Repair*
Dose-Response Relationship, Radiation
Neoplasm Metastasis / pathology
Radiation Tolerance / radiation effects*
Rats, Inbred Strains
Time Factors
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/Tumor Suppressor Protein p53

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