Abstract
The ability of adriamycin to inhibit Z-DNA formation induced by a high-salt environment was investigated. ADM inhibited this conversion, such that in poly (dG-dC) total inhibition was observed at 1 ADM: 9 base pairs and in eukaryotic DNA (calf thymus) at 1 ADM: 11,5 base pairs. Even at low ADM concentration, 1 ADM: 160 base pairs, some inhibition was observed. At similar ADM:DNA concentrations, an inhibition in DNA synthesis in cells in culture was observed, which showed some parallel with the inhibition of Z-DNA formation. A model is proposed where Z-DNA formation precedes DNA synthesis and where inhibition of the former could explain the antineoplastic nature of adriamycin.
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Selected References
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- Fialkoff H., Goodman M. F., Seraydarian M. W. Differential effect of adriamycin on DNA replicative and repair synthesis in cultured neonatal rat cardiac cells. Cancer Res. 1979 Apr;39(4):1321–1327. [PubMed] [Google Scholar]
- Haniford D. B., Pulleyblank D. E. Facile transition of poly[d(TG) x d(CA)] into a left-handed helix in physiological conditions. Nature. 1983 Apr 14;302(5909):632–634. doi: 10.1038/302632a0. [DOI] [PubMed] [Google Scholar]
- Mirau P. A., Kearns D. R. The effect of intercalating drugs on the kinetics of the B to Z transition of poly(dG-dC). Nucleic Acids Res. 1983 Mar 25;11(6):1931–1941. doi: 10.1093/nar/11.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgenegg G., Celio M. R., Malfoy B., Leng M., Kuenzle C. C. Z-DNA immunoreactivity in rat tissues. Nature. 1983 Jun 9;303(5917):540–543. doi: 10.1038/303540a0. [DOI] [PubMed] [Google Scholar]
- Nakata Y., Hopfinger A. J. Predicted mode of intercalation of doxorubicin with dinucleotide dimers. Biochem Biophys Res Commun. 1980 Jul 31;95(2):583–588. doi: 10.1016/0006-291x(80)90824-4. [DOI] [PubMed] [Google Scholar]
- Neidle S. New twists to left-handed DNA. Nature. 1983 Apr 14;302(5909):574–574. doi: 10.1038/302574a0. [DOI] [PubMed] [Google Scholar]
- Nordheim A., Pardue M. L., Lafer E. M., Möller A., Stollar B. D., Rich A. Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes. Nature. 1981 Dec 3;294(5840):417–422. doi: 10.1038/294417a0. [DOI] [PubMed] [Google Scholar]
- Santoro C., Costanzo F. Stretches of alternating poly(T-dG), with the capacity to form Z-DNA, are present in human liver transcripts. FEBS Lett. 1983 May 2;155(1):69–72. doi: 10.1016/0014-5793(83)80211-7. [DOI] [PubMed] [Google Scholar]
- Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
- Van Helden P. D., Wild I. J. Effects of adriamycin on heart and skeletal muscle chromatin. Biochem Pharmacol. 1982 Mar 15;31(6):973–977. doi: 10.1016/0006-2952(82)90330-6. [DOI] [PubMed] [Google Scholar]
- Viegas-Péquignot E., Derbin C., Lemeunier F., Taillandier E. Identification of left-handed Z-DNA by indirect immunomethods in metaphasic chromosomes of a mammal, Gerbillus nigeriae (Gerbillidae, Rodentia). Ann Genet. 1982;25(4):218–222. [PubMed] [Google Scholar]
- Yu F. L. Actinomycin D-binding in vivo: active chromatin preferred. FEBS Lett. 1983 May 30;156(1):83–87. doi: 10.1016/0014-5793(83)80253-1. [DOI] [PubMed] [Google Scholar]
- Zähringer J., Höfling B., Raum W., Kandolph R. Effect of adriamycin on the polyribosome and messenger-RNA content of rat heart muscle. Biochim Biophys Acta. 1980 Jul 29;608(2):315–323. doi: 10.1016/0005-2787(80)90177-x. [DOI] [PubMed] [Google Scholar]
- Zähringer J., Höfling B., Raum W., Kandolph R. Effect of adriamycin on the polyribosome and messenger-RNA content of rat heart muscle. Biochim Biophys Acta. 1980 Jul 29;608(2):315–323. doi: 10.1016/0005-2787(80)90177-x. [DOI] [PubMed] [Google Scholar]