Chromatid breakage: Differential effect of inhibitors of DNA synthesis during G₂ phase

The cell cycle specificity of chromatid breakage induced by inhibitors of DNA synthesis depends on the mechanism of drug action. 5-Hydroxy-2- formylpyridine thiosemicarbazone, hydroxyurea, and guanazole, compounds that inhibit ribonucleotide reductase, do not cause chromatid breakage during G ₂ phase. In contrast, two active antitumor agents, arabinosylcytosine and 5-azacytidine, which are either incorporated into polynucleotides or affect DNA polymerase, produce chromatid breakage during Gg phase. All of these agents except guanazole also induce breakage in S phase.