Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1988 Aug 11;16(15):7663–7672.

Reactivity of monofunctional cis-platinum adducts as a function of DNA sequence.

J M Malinge 1, M Leng 1
PMCID: PMC338433  PMID: 3137529

Abstract

The purpose of this work was to study the chemical reactivity of monofunctional cis-platinum-nucleic acid adducts as a function of nucleic acid sequence. The first part of the paper deals with the formation of these adducts. It is shown that the ternary nucleic acid-cis-platinum-ethidium bromide complexes in which ethidium bromide and nucleotide residues are cross-linked by cis-platinum, are relatively unstable at 37 degrees C. In the presence of acridine, ethidium bromide (but not cis-platinum) is slowly released which leads to the formation of monofunctional cis-platinum-nucleic acid adducts. After removal of acridine, the monofunctional adducts react further to become bifunctional. The second part of the paper deals with the kinetics of disappearance of the monofunctional adducts in several polynucleotides but not in poly(dG).poly(dC). When the adducts possess a chloride ligand, the limiting step in the cross-linking is the rate of aquation reaction of the chloride ligand. The rate constants are an order of magnitude larger when the monofunctional adducts do not possess a chloride ligand. In both the cases, the rate constants are apparently independent of the nucleic acid sequence.

Full text

PDF
7663

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bowler B. E., Lippard S. J. Modulation of platinum antitumor drug binding to DNA by linked and free intercalators. Biochemistry. 1986 May 20;25(10):3031–3038. doi: 10.1021/bi00358a044. [DOI] [PubMed] [Google Scholar]
  2. Bradley M. O., Patterson S., Zwelling L. A. Thiourea prevents cytotoxicity and mutagenicity, but not sister-chromated exchanges in V79 cells treated with cis-diaminedichloroplatinum (II). Mutat Res. 1982 Sep;96(1):67–74. doi: 10.1016/0027-5107(82)90017-3. [DOI] [PubMed] [Google Scholar]
  3. Butour J. L., Johnson N. P. Chemical reactivity of monofunctional platinum-DNA adducts. Biochemistry. 1986 Aug 12;25(16):4534–4539. doi: 10.1021/bi00364a012. [DOI] [PubMed] [Google Scholar]
  4. Castleman H., Hanau L. H., Erlanger B. F. Stabilization of (dG-dC)n.(dG-dC)n in the Z conformation by a crosslinking reaction. Nucleic Acids Res. 1983 Dec 10;11(23):8421–8429. doi: 10.1093/nar/11.23.8421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eastman A. Characterization of the adducts produced in DNA by cis-diamminedichloroplatinum(II) and cis-dichloro(ethylenediamine)platinum(II). Biochemistry. 1983 Aug 2;22(16):3927–3933. doi: 10.1021/bi00285a031. [DOI] [PubMed] [Google Scholar]
  6. Eastman A. Reevaluation of interaction of cis-dichloro(ethylenediamine)platinum(II) with DNA. Biochemistry. 1986 Jul 1;25(13):3912–3915. doi: 10.1021/bi00361a026. [DOI] [PubMed] [Google Scholar]
  7. Eastman A. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther. 1987;34(2):155–166. doi: 10.1016/0163-7258(87)90009-x. [DOI] [PubMed] [Google Scholar]
  8. Fichtinger-Schepman A. M., van der Veer J. L., den Hartog J. H., Lohman P. H., Reedijk J. Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. Biochemistry. 1985 Jan 29;24(3):707–713. doi: 10.1021/bi00324a025. [DOI] [PubMed] [Google Scholar]
  9. Knox R. J., Friedlos F., Lydall D. A., Roberts J. J. Mechanism of cytotoxicity of anticancer platinum drugs: evidence that cis-diamminedichloroplatinum(II) and cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) differ only in the kinetics of their interaction with DNA. Cancer Res. 1986 Apr;46(4 Pt 2):1972–1979. [PubMed] [Google Scholar]
  10. Malfoy B., Hartmann B., Macquet J. P., Leng M. Immunochemical studies of DNA modified by cis-dichlorodiammineplatinum(II) in vivo and in vitro. Cancer Res. 1981 Oct;41(10):4127–4131. [PubMed] [Google Scholar]
  11. Malinge J. M., Leng M. Reaction of nucleic acids and cis-diamminedichloroplatinum(II) in the presence of intercalating agents. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6317–6321. doi: 10.1073/pnas.83.17.6317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Malinge J. M., Schwartz A., Leng M. Characterization of the ternary complexes formed in the reaction of cis-diamminedichloroplatinum (II), ethidium bromide and nucleic acids. Nucleic Acids Res. 1987 Feb 25;15(4):1779–1797. doi: 10.1093/nar/15.4.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mascharak P. K., Sugiura Y., Kuwahara J., Suzuki T., Lippard S. J. 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 U S A. 1983 Nov;80(22):6795–6798. doi: 10.1073/pnas.80.22.6795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Micetich K., Zwelling L. A., Kohn K. W. Quenching of DNA:platinum(II) monoadducts as a possible mechanism of resistance to cis-diamminedichloroplatinum(II) in L1210 cells. Cancer Res. 1983 Aug;43(8):3609–3613. [PubMed] [Google Scholar]
  15. Morgan A. R., Coulter M. B., Flintoff W. F., Paetkau V. H. Enzymatic synthesis of deoxyribonucleic acids with repeating sequences. A new repeating trinucleotide deoxyribonucleic acid, d(T-C-C)n-d(G-G-A)n. Biochemistry. 1974 Apr 9;13(8):1596–1603. doi: 10.1021/bi00705a007. [DOI] [PubMed] [Google Scholar]
  16. Rahmouni A., Malinge J. M., Schwartz A., Leng M. Comparison between poly(dG-dC).poly(dG-dC) and DNA modified by cis-diamminedichloroplatinum (II): immunological and spectroscopic studies. J Biomol Struct Dyn. 1985 Oct;3(2):363–375. doi: 10.1080/07391102.1985.10508423. [DOI] [PubMed] [Google Scholar]
  17. Roberts J. J., Thomson A. J. The mechanism of action of antitumor platinum compounds. Prog Nucleic Acid Res Mol Biol. 1979;22:71–133. doi: 10.1016/s0079-6603(08)60799-0. [DOI] [PubMed] [Google Scholar]
  18. Schaller W., Reisner H., Holler E. Kinetic investigation of the DNA platination reaction: evidence for a transient adduct between deoxyribonucleic acid and cis-platinum(II). Biochemistry. 1987 Feb 10;26(3):943–950. doi: 10.1021/bi00377a039. [DOI] [PubMed] [Google Scholar]
  19. Segal E., Le Pecq J. B. Role of ligand exchange processes in the reaction kinetics of the antitumor drug cis-diamminedichloroplatinum(II) with its targets. Cancer Res. 1985 Feb;45(2):492–498. [PubMed] [Google Scholar]
  20. Tullius T. D., Lippard S. J. Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II). Proc Natl Acad Sci U S A. 1982 Jun;79(11):3489–3492. doi: 10.1073/pnas.79.11.3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zwelling L. A., Filipski J., Kohn K. W. Effect of thiourea on survival and DNA cross-link formation in cells treated with platinum(II) complexes, L-phenylalanine mustard, and bis(2-chloroethyl)methylamine. Cancer Res. 1979 Dec;39(12):4989–4995. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES