Differential response of mitochondrial and nuclear DNA syntheses to hydroxyurea in normal and regenerating rat liver

Male rats were injected with hydroxyurea (100 mg/kg or 500 mg/kg) and sacrificed at different times after injection. [¹⁴C]-thymidine is injected 1 hr before sacrifice and the specific radioactivity determined in total DNA of spleen, thymus and regenerating liver and in nuclear and mitochondrial DNA of normal and regenerating liver. Total DNA synthesis is rapidly inhibited in lymphoid tissues and in regenerating liver, but recovery is more rapid in the latter organ. Inhibition of DNA synthesis occurs more slowly in the mitochondria than in the nuclei of normal and regenerating liver; the rate of recovery is also lower in the mitochondria. These differences between the two DNA are tentatively ascribed to a less rapid exhaustion of the intra-mitochondrial pool of deoxynucleotides as regards the inhibition phase, and to a competition for the precursor pool between N-DNA and M-DNA syntheses, in favor of the predominant one (N-DNA synthesis) as regards the recovery phase.