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. 1991 Jul;64(1):29–34. doi: 10.1038/bjc.1991.234

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

P Muus 1, C Van den Bogert 1, H De Vries 1, A Pennings 1, M Holtrop 1, C Haanen 1
PMCID: PMC1977335  PMID: 1649619

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.

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Selected References

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