Bromodeoxyuridine-induced sister chromatid exchanges in human lymphocytes.

Abstract

Human lymphocytes were cultivated for 75 hours in the presence of various concentrations of bromodeoxyuridine (BrdU). The cells were stained with the fluorochrome Hoechst 33258 plus Giemsa. Cells in the first, second and third division could be distinguished, as well as sister chromatid exchanges (SCE) and centromeric exchanges (CME). BrdU-concentrations higher than 100 μM decreased the relative number of cells in the third division and increased the number of cells in the first division in vitro, indicating that higher BrdU-concentrations considerably inhibit cell propagation. The frequency of SCE and CME increased significantly for each stepwise rise in the BrdU concentration between 20–500 μM, suggesting that the vast majority of SCE and CME are induced by BrdU. The average frequency of SCE per cell in 100 μM of BrdU ranged between 18–28 for 8 control subjects with a group mean of 22.2±3.4. BrdU-induced SCE were found to be equally distributed between chromosomes in relation to their lengths while the frequency of CME was independent of chromosome length. High concentrations of BrdU (200–500 μM) significantly increased the number of chromosome aberrations in the cells of all of four subjects investigated. The aberrations were mainly chromosome breaks.