1-beta-D-arabinofuranosylcytosine (Ara-C) enhances mitochondrial activities in human leukaemic cells.

Abstract

1-beta-D-Arabinofuranosylcytosine (Ara-C) at a concentration which inhibits nuclear-DNA reduplication (0.05 microM), enhances mitochondrial activities like respiration, in cell of a human leukaemic cell line Molt 4. While the specific activity of cytochrome c oxidase doubles in the course of the G1 phase of the cell cycle in control cells, in the presence of Ara-C G1 phase cells begin to increase the enzyme activity earlier and show a 3-fold rise of the enzyme activity in the same period of time. This is explained by an enhanced expression of the mitochondrial genome: the concentration of transcripts for the mitochondrially encoded subunit II of cytochrome c oxidase increases. Inhibition of mitochondrial protein synthesis abolishes the Ara-C induced effect on the specific activity of cytochrome c oxidase activity. The concentration of transcripts of the nuclearly encoded subunit IV of cytochrome c oxidase is the same as in control cells, and also the specific activity of the mitochondrial enzyme citrate synthase, which is exclusively encoded on nuclear-DNA, is not affected by Ara-C. Dysregulation in time and intensity of the expression of the mitochondrial relative to the nuclear genome may impair cell function and reflect a till now neglected mechanism of Ara-C cytotoxicity.