Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: Impact of DNA repair

• Published in: International journal of radiation biology 2008-01, Vol.84 (7), p.533-548
• Main Authors: Thomas, Charles, Charrier, Josiane, Massart, Catherine, Cherel, Michel, Fertil, Bernard, Barbet, Jacques, Foray, Nicolas
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - radiation effects; Bioengineering; cell cycle; Cell Cycle - radiation effects; cell death; Cell Line, Tumor; Colonic Neoplasms - pathology; DNA Breaks, Double-Stranded - radiation effects; DNA Breaks, Single-Stranded - radiation effects; DNA Repair; Dose-Response Relationship, Radiation; Life Sciences; Low-dose hyper-radiosensitivity; micrometastases; Neoplasm Metastasis - pathology; Nuclear medicine; Phosphorylation; Radiation Tolerance - radiation effects; Rats; Rats, Inbred Strains; Time Factors; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/09553000802195331

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 G1 cells and RAD51-dependent repair that targets S-G2 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.