¹Bute Medical School, Bute Medical Buildings, University of St Andrews, St Andrews KY16 9TS, Scotland, UK

Correspondence: Dr PE Bryant, University of St Andrews, Bute Medical School, St Andrews, Fife KY16 9TS, UK. E-mail: peb@st-and.ac.uk

Received 8 February 2008; Revised 25 April 2008; Accepted 20 June 2008; Published online 29 July 2008.

Abstract

Chromatid breaks in cells exposed to low dose irradiation are thought to be initiated by DNA double-strand breaks (DSB), and the frequency of chromatid breaks has been shown to increase in DSB rejoining deficient cells. However, the underlying causes of the wide variation in frequencies of G2 chromatid breaks (or chromatid 'radiosensitivity') in irradiated T-lymphocytes from different normal individuals and cancer cases are as yet unclear. Here we report evidence that topoisomerase II expression level is a factor determining chromatid radiosensitivity. We have exposed the promyelocytic leukaemic cell line (HL60) and two derived variant cell lines (MX1 and MX2) that have acquired resistance to mitoxantrone and low expression of topoisomerase II , to low doses of -radiation and scored the induced chromatid breaks. Chromatid break frequencies were found to be significantly lower in the variant cell lines, compared with their parental HL60 cell line. Rejoining of DSB in the variant cell lines was similar to that in the parental HL60 strain. Our results indicate the indirect involvement of topoisomerase II in the formation of radiation-induced chromatid breaks from DSB, and suggest topoisomerase II as a possible factor in the inter-individual variation in chromatid radiosensitivity.