Catalytic inhibition of topoisomerase II in Werner's syndrome cell lines enhances chromosomal damage induced by X-rays in the G2 phase of the cell cycle.
OBJECTIVE
To investigate whether catalytic topoisomerase II activity by ICRF187, a compound that interferes with the catalytic cycle of topoisomerase II without causing DNA damage, could result in a modulation of X-ray-induced chromosomal damage in Werner's syndrome (WS) cell lines.


METHODS
Two WS (KO375, DJG) and one normal lymphoblastoid cell line (SNW646) were exposed to X-rays, post-treated with ICRF187 and harvested after various recovery times. Cell progression to mitosis was monitored by 5-bromo-2'-deoxyuridine (BrdUrd) and fluorescent immmunodetection to analyse chromosomal damage in homogeneous treated cell populations in the G1, S or G2 phase of the cell cycle.


RESULTS
In WS cell lines, catalytic inhibition of topoisomerase II activity by ICRF187 resulted in potentiation of X-ray- induced chromosomal damage in the G2 phase of the cell cycle. This potentiation was not observed in the G1 or S phases of the cell cycle, neither in WS nor normal cells.


CONCLUSIONS
These results point out the possibility that Werner's syndrome protein (WRNp) might play a role in a G2 recombinational pathway of double-strand break repair, cooperating with topoisomerase II and thus contributing to maintain genomic integrity.
Dipartimento di Agrobiologia ed Agrochimica Università degli Studi della Tuscia, Viterbo, Italy.
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Palitti
D002384:Catalysis; D002460:Cell Line; D002869:Chromosome Aberrations; D004249:DNA Damage; D016195:G2 Phase / Q000528:radiation effects*; D006801:Humans; D011929:Razoxane / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors; D014898:Werner Syndrome / Q000235:genetics*; D014965:X-Rays
D059005:Topoisomerase II Inhibitors; D011929:Razoxane