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. 1984 Jan;3(1):11–16. doi: 10.1002/j.1460-2075.1984.tb01754.x

Inhibition of the reactions catalysed by a type I topoisomerase and catenating enzyme of Trypanosoma cruzi by DNA-intercalating drugs. Preferential inhibition of the catenating reaction.

S Douc-Rasy, A Kayser, G F Riou
PMCID: PMC557290  PMID: 6323159

Abstract

A catenating enzyme and a type I topoisomerase were purified from Trypanosoma cruzi. We investigated the inhibitory effect of DNA-intercalating drugs on topoisomerisations catalysed by these enzymes. Inhibition of catenation was detected by electrophoretic analysis in neutral agarose gels. However, the inhibition of relaxation was not readily detectable in these gels since supercoiled DNA, which was relaxed in the presence of an intercalating drug, returned to a supercoiled state when the drug was removed. Thus electrophoretic analyses were made in gels containing chloroquine so that unreacted DNA could be distinguished from DNA relaxed by the enzyme. The results show that the catenation was more sensitive to DNA-intercalating drugs than the relaxation.

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Selected References

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  1. BROWNLEE G., GOSS M. D., GOODWIN L. G., WOODBINE M., WALLS L. P. The chemotherapeutic action of phenanthridine compounds. I. Trypanosoma congolense and Trypanosoma rhodesiense. Br J Pharmacol Chemother. 1950 Jun;5(2):261–276. doi: 10.1111/j.1476-5381.1950.tb01012.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bénard J., Dat-Xuong N., Riou G. Activité trypanocide de quelques dérivés de l'ellipticine sur Trypanosoma cruzi cultivé in vitro. C R Acad Sci Hebd Seances Acad Sci D. 1975 Mar 3;280(9):1177–1180. [PubMed] [Google Scholar]
  3. Clercq E. D., Dann O. Diaryl amidine derivatives as oncornaviral DNA polymerase inhibitors. J Med Chem. 1980 Jul;23(7):787–795. doi: 10.1021/jm00181a016. [DOI] [PubMed] [Google Scholar]
  4. Crick F. H., Wang J. C., Bauer W. R. Is DNA really a double helix? J Mol Biol. 1979 Apr 15;129(3):449–457. doi: 10.1016/0022-2836(79)90506-0. [DOI] [PubMed] [Google Scholar]
  5. Douc-Rasy S., Multon E., Kayser A., Riou G. Inhibition par les dérivés de l'ellipticine des réactions catalysées par les topoisomérases: inhibition préférentielle d'une topoisomérase II. C R Seances Acad Sci III. 1983;296(19):899–904. [PubMed] [Google Scholar]
  6. Gaugain B., Barbet J., Capelle N., Roques B. P., Le Pecq J. B. DNA Bifunctional intercalators. 2. Fluorescence properties and DNA binding interaction of an ethidium homodimer and an acridine ethidium heterodimer. Biochemistry. 1978 Nov 28;17(24):5078–5088. doi: 10.1021/bi00617a002. [DOI] [PubMed] [Google Scholar]
  7. Gellert M. DNA topoisomerases. Annu Rev Biochem. 1981;50:879–910. doi: 10.1146/annurev.bi.50.070181.004311. [DOI] [PubMed] [Google Scholar]
  8. Jones R. L., Davidson M. W., Wilson W. D. Comparative viscometric analysis of the interaction of chloroquine and quinacrine with superhelical and sonicated DNA. Biochim Biophys Acta. 1979 Jan 26;561(1):77–84. doi: 10.1016/0005-2787(79)90492-1. [DOI] [PubMed] [Google Scholar]
  9. Keller W. Characterization of purified DNA-relaxing enzyme from human tissue culture cells. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2550–2554. doi: 10.1073/pnas.72.7.2550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Le Pecq J. B., Nguyen-Dat-Xuong, Gosse C., Paoletti C. A new antitumoral agent: 9-hydroxyellipticine. Possibility of a rational design of anticancerous drugs in the series of DNA intercalating drugs. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5078–5082. doi: 10.1073/pnas.71.12.5078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Paoletti C., Le Pecq J. B., Dat-Xuong N., Juret P., Garnier H., Amiel J. L., Rouesse J. Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137). Recent Results Cancer Res. 1980;74:107–123. doi: 10.1007/978-3-642-81488-4_15. [DOI] [PubMed] [Google Scholar]
  12. Pelaprat D., Delbarre A., Le Guen I., Roques B. P., Le Pecq J. B. DNA intercalating compounds as potential antitumor agents. 2. Preparation and properties of 7H-pyridocarbazole dimers. J Med Chem. 1980 Dec;23(12):1336–1343. doi: 10.1021/jm00186a010. [DOI] [PubMed] [Google Scholar]
  13. Pelaprat D., Oberlin R., Le Guen I., Roques B. P., Le Pecq J. B. DNA intercalating compounds as potential antitumor agents. 1. Preparation and properties of 7H-pyridocarbazoles. J Med Chem. 1980 Dec;23(12):1330–1335. doi: 10.1021/jm00186a009. [DOI] [PubMed] [Google Scholar]
  14. Pulleyblank D. E., Shure M., Tang D., Vinograd J., Vosberg H. P. Action of nicking-closing enzyme on supercoiled and nonsupercoiled closed circular DNA: formation of a Boltzmann distribution of topological isomers. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4280–4284. doi: 10.1073/pnas.72.11.4280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Riou G. F., Gabillot M., Douc-Rasy S., Kayser A., Barrois M. A type I DNA topoisomerase from Trypanosoma cruzi. Eur J Biochem. 1983 Aug 15;134(3):479–484. doi: 10.1111/j.1432-1033.1983.tb07592.x. [DOI] [PubMed] [Google Scholar]
  16. Riou G. F., Gutteridge W. E. Comparative study of kinetoplast DNA in culture, blood and intracellular forms of Trypanosoma cruzi. Biochimie. 1978;60(4):365–379. doi: 10.1016/s0300-9084(78)80670-1. [DOI] [PubMed] [Google Scholar]
  17. Riou G., Gabillot M., Douc-Rasy S., Kayser A. Purification partielle et caractérisation de DNA-topoisomérases nucléaires de trypanosomes. C R Seances Acad Sci III. 1982 Mar 15;294(11):439–442. [PubMed] [Google Scholar]
  18. Roques B. P., Pelaprat D., Le Guen I., Porcher G., Gosse C., Le Pecq J. B. DNA bifunctional intercalators: antileukemic activity of new pyridocarbazole dimers. Biochem Pharmacol. 1979 Jun 1;28(11):1811–1815. doi: 10.1016/0006-2952(79)90547-1. [DOI] [PubMed] [Google Scholar]
  19. Shure M., Pulleyblank D. E., Vinograd J. The problems of eukaryotic and prokaryotic DNA packaging and in vivo conformation posed by superhelix density heterogeneity. Nucleic Acids Res. 1977;4(5):1183–1205. doi: 10.1093/nar/4.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]

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