Effects of Hoechst 33258 on different cell cycle events: I. Inhibition of synthetic activities in bone-marrow cells of the mole rat Bandicota bengalensis

Abstract

A study of the effects of the A-T base-specific ligand Hoechst 33258 on the cell cycle events of the bone-marrow cells of the mole rat Bandicota bengalensis reveals that (1) the G2 phase is prolonged by 2 h; (2) the chromosomes are undercondensed to varying degrees in about 30% metaphases; (3) DNA as well as RNA synthesis is partially inhibited. Study on DNA fibre autoradiograms shows that despite the inhibition of DNA synthesis the average replicon size and rate of fork migration remain unchanged, but there is a marked asynchrony of initiation of replicons in replicon clusters in H-treated cells in comparison with control. It is suggested that these inhibitory effects result from the stabilization of the double-stranded organization of DNA (dsDNA) by the drug so that the unwinding of DNA at the replication or transcription origin sites is greatly impaired. It is likely that this introduces asynchrony in the initiation of replicons within replicon clusters which may retard the overall rate of replication. In addition, it appears that the reduction in transcription is at least one cause for the prolongation of G2 phase.