Inhibition of bromodeoxyuridine-associated sister chromatid exchanges in Bloom's syndrome cells with cycloheximide

Abstract

Effects of cycloheximide (CH) and deoxycytidine (dC) on the frequency of sister chromatid exchanges (SCEs) in normal and Bloom's syndrome (BS) cells labeled with bromodeoxyuridine (BrdU) during first, second, and third cell cycles were evaluated using endomitotic and three-way differentiation analyses. When CH at 0.2 and 2.0 ng/ml was added to normal and BS cultures of BrdU-labeled endomitoses, the rate of single SCEs was significantly decreased in BS cells, though the rate of reduction in single SCEs was slight in normal cells. No significant change was detected in the twin SCE rate. In BS cells, treatment with CH at 0.2 and 2.0 ng/ml produced significant reductions in SCEs in both the second (SCE 2) and third (SCE 3) cell cycles, sometimes reaching the normal level. Treatment with dC at 13 and 26 μg/ml resulted in almost no significant changes in rates of SCE during first, second, and third cell cycles. When CH was added to BrdU-labeled normal and BS cell cultures, the cell growth rates improved from 35% to 70% over the control level in the BS cells, though in normal cells, the addition of CH resulted in a close-dependent lower cell growth rate. Deoxycytidine did not noticeably affect the cell growth rates in BrdU-labeled normal and BS cultures. The finding that the reduction of BrdU-induced SCEs in BS is paralleled by cell growth improvement is of special interest.