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Incorporation of thymidine into nuclear and mitochondrial DNA has been measured in the livers of normal rats and of rats killed 17 h or 24 h after partial hepatectomy. When total-body X-irradiation (500 or 1,500 R) is given at increasing intervals (up to 30 h) before sacrifice, a progressive decrease followed by a plateau of low level of incorporation is observed in the nuclear DNA (N-DNA) whereas the synthesis of mitochondrial DNA (M-DNA) first decreases until a minimal value is reached after 4 h in normal liver and 12 h in regenerating liver, then recovers at an exponential rate, quite independently of the nuclear DNA synthesis. The results suggest that irradiation can interfere with the enzymatic processes of both M-DNA and N-DNA syntheses, but that the persistence of the inhibition of N-DNA synthesis must be ascribed to a temporary block in the cell cycle. The SH-protector AET injected to non-irradiated rats exerts a very small inhibitory effect on normal liver N-DNA and M-DNA synthesis. In regenerating liver, both syntheses are affected rather similarly suggesting a common mechanism of inhibition through impairment of some step in the synthetic process.

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.