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

Abstract：

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.

journal_name

Int J Radiat Biol

journal_title

International journal of radiation biology

authors

Thomas C,Charrier J,Massart C,Cherel M,Fertil B,Barbet J,Foray N

doi

10.1080/09553000802195331

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

533-48

issue

7

eissn

0955-3002

issn

1362-3095

pii

795327857

journal_volume

84

pub_type

杂志文章

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