Reactivity of DNA and cis-Diamminedichloroplatinumul(II) in the Presence of Intercalating Agents

  • Frederic Gaucheron
  • Marie-Agnes Lemaire
  • Jean Marc Malinge
  • Annie Schwartz
  • Marc Leng

Abstract

The antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) is assumed to exhibit its toxicity by reacting with cellular DNA. Lesions produced in DNA have been characterized as bifunctional adducts including mainly intrastrand and interstrand cross-links. It is not yet known which lesion(s) is(are) responsible for selective destruction of tumor cells1–3. Drugs known to bind to DNA such as doxorubicin or bleomycin are commonly used therapeutically in combination with cis-DDP4. In vitro several studies have shown the mutual influence of cis-DDP and drugs binding to DNA5–11. One purpose of our work is to better understand how the binding of cis-DDP can be altered by the presence of other drugs interacting also with DNA. In this paper, we first show that RNA polymerases are a convenient tool to detect the adducts formed in the in vitro reaction between DNA and cis-DDP. In particular, we find that the interstrand adducts are formed at the d(GC) sites. Then, we show that a new kind of adduct, a DNA-monocoordinated complex, is formed when the reaction of platination is done in the presence of some intercalating agents. In this reaction, the DNA double helix first favors the formation of the new adduct and then favors the release of a platinum derivative. These results are discussed in relation with a catalytic activity of the DNA double helix.

Keywords

Antitumor Drug Intercalate Agent Sodium Cyanide Guanine Residue Bleomycin Cleavage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    A. Eastman, The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes, Pharmac. Ther. 34:155 (1987).CrossRefGoogle Scholar
  2. 2.
    J. Reedijk, The mechanism of action of platinum anti-tumor drugs, Pure and Appl. Chem. 59:181 (1987).CrossRefGoogle Scholar
  3. 3.
    S.J. Lippard, Chemistry and molecular biology of platinum anticancer drugs, Pure and Appl. Chem. 59:731 (1987).CrossRefGoogle Scholar
  4. 4.
    A.W. Prestayko, S.T. Crooke and S.K. Carter, “Cisplatin: Current Status and New Developments”, Academic Press, New York (1980).Google Scholar
  5. 5.
    P.K. Mascharak, Y. Sugiura, J. Kuwahara, T. Suzuki, and S.J. Lippard, Alteration and activation of sequence-specific cleavage of DNA by bleomycin in the presence of the antitumor drug cis-diamminedichloroplatinum(II), Proc. Natl. Acad. Sci. USA 80:6795 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    B. Gold, V. Dange, M.A. Moore, A. Eastman, G.A. Van der Marel, J.H. VanVan der Boom, and S.M. Hecht, Alteration of bleomycin cleavage in a platinated DNA oligomer of defined structure, J. Am. Chem. Soc. 110:2347 (1988).CrossRefGoogle Scholar
  7. 7.
    T.D. Tullius and S.J. Lippard, Ethidium bromide changes the nuclease-sensitive DNA binding sites of antitumor drug cis-diamminedichloroplatinum(II), Proc. Natl. Acad. Sci. USA 79:3489 (1982).PubMedCrossRefGoogle Scholar
  8. 8.
    B.E. Bowler and S.J. Lippard, Modulation of platinum antitumor drug binding to DNA by linked and free intercalator, Biochemistry 25:3031 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    J.M. Malinge and M. Leng, Reaction of nucleic acids and cis-diamminedichloroplatinum(II) in the presence of intercalating agents, Proc. Natl. Acad. Sci. USA 83:6317 (1986).PubMedCrossRefGoogle Scholar
  10. 10.
    J.M. Malinge, A. Schwartz and M. Leng, Characterization of the ternary complexes formed in the reaction of cis-diamminedichloroplatinum(II), ethidium bromide and nucleic acids, Nucleic Acids Res. 15:1779 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    W.I. Sundquist, D.P. Bancroft, L. Chassot and S.J. Lippart, DNA promotes the reaction of cis-diamminedichloroplatinum(IIII) with the exocyclic amino groups of ethidium bromide, J. Am. Chem. Soc. 110:8559 (1988).CrossRefGoogle Scholar
  12. 12.
    V.D. Axelrod and F.R. Kramer, Transcription from bacteriophage T7 and SP6 RNA polymerase promoters in the presence of 3′-deoxyribonucleoside 5′-triphosphate chain terminator, Biochemistry 24:5716 (1985).PubMedCrossRefGoogle Scholar
  13. 13.
    H. Htun and J. Dahlberg, Single strands, triple strands, and kinks in H-DNA, Science 241:1791 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    J.S. Lippard and J.D. Hoeschle, Binding of the antitumor drug cis-diamminedichloroplatinum(II) to DNA and to the nucleosome core particle, Proc. Natl. Acad. Sci. USA 76:6091 (1979).PubMedCrossRefGoogle Scholar
  15. 15.
    A. Schwartz, M. Sip and M. Leng, Sodium cyanide: a chemical probe of the conformation of DNA modified by the antitumor drug cis-diamminedichloroplatinum(II), J. Am. Chem. Soc. 112:3673 (1990).CrossRefGoogle Scholar
  16. 16.
    S.J. Lippard, H.M. Ushay, C.M. Merkel and M. Poirier, Use of antibodies to probe stereochemistry of antitumor platinum drug binding to deoxyribonucleic acid, Biochemistry 22:5165 (1983).CrossRefGoogle Scholar
  17. 17.
    M.A. Lemaire, A. Schwartz, R. Rahmouni and M. Leng, Interstrand crosslinks are preferentially formed at the d(GC) sites in the reaction between cis-diamminedichloroplatinum(IIII) and DNA, Proc. Natl. Acad. Sci. USA, in press.Google Scholar
  18. 18.
    J.M. Malinge, M. Sip, A.J. Blacker, J.M. Lehn and M. Leng, Formation of a DNA monofunctional cis-platinum adduct cross-linking the intercalating drug N-methyl-2,7-diazapyrenium, Nucleic Acids Res. 18:3887 (1990).PubMedCrossRefGoogle Scholar
  19. 19.
    F. Gaucheron, J.M. Malinge, A.J. Blacker, J.M. Lehn and M. Leng, Possible DNA catalytic activity in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) and the intercalator N-methyl-2,7-diazapyrenium, Proc. Natl. Acad. Sci. USA, in press.Google Scholar
  20. 20.
    C.M. Sorenson and A. Eastman, Mechanism of cis-diamminedichloroplatinum(II)-induced cytotoxicity: role of G2 arrest and DNA double-strand breaks, Cancer Res. 48:4484 (1988).PubMedGoogle Scholar
  21. 21.
    Y. Corda, C. Job, M.F. Anin, M. Leng and D. Job, Transcription by eucaryotic and procaryotic RNA polymerases of DNA modified at a d(GG) or a d(AG) site by the antitumor drug cis-diamminedichloroplatinum (II), Biochemistry 30:222 (1991).PubMedCrossRefGoogle Scholar
  22. 22.
    L.S. Hollis, A.R. Amundsen and A.W. Stern, Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis[Pt(NH3)2(N-donor)Cl]+, J. Med. Chem. 32:1218 (1989).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Frederic Gaucheron
    • 1
  • Marie-Agnes Lemaire
    • 1
  • Jean Marc Malinge
    • 1
  • Annie Schwartz
    • 1
  • Marc Leng
    • 1
  1. 1.Centre de Biophysique MoléculaireC.N.R.S., 1AOrléans cedex 2France

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