title: Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: impact of DNA repair.
abstract: OBJECTIVE
  To ask whether highly metastatic sublines show more marked low-dose hyper-radiosensitivity (HRS) response than poorly metastatic ones.
  
  
  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.
authors.affiliation: Institut National de la Sante et de la Recherche Medicale (INSERM), U601, Nantes, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Thomas
authors.forename: Josiane
authors.initials: J
authors.lastname: Charrier
authors.forename: Catherine
authors.initials: C
authors.lastname: Massart
authors.forename: Michel
authors.initials: M
authors.lastname: Cherel
authors.forename: Bernard
authors.initials: B
authors.lastname: Fertil
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foray
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D053904:DNA Breaks, Single-Stranded / Q000528:radiation effects*; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D009362:Neoplasm Metastasis / Q000473:pathology; D010766:Phosphorylation; D011836:Radiation Tolerance / Q000528:radiation effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53