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. 1992 Sep 25;20(18):4825–4830. doi: 10.1093/nar/20.18.4825

Lability of monofunctional cis-platinum adducts: role of DNA double helix.

M F Anin 1, F Gaucheron 1, M Leng 1
PMCID: PMC334238  PMID: 1408797

Abstract

Recently, we have shown that the adduct formed in the reaction between the platinum-triamine complex cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)Cl]2+ and one single-stranded oligonucleotide was stable but became labile as soon as the platinated oligonucleotide was paired with its complementary strand (Gaucheron et al. Proc. Natl. Acad. Sci. USA 88, 3516-3519 (1991)). To generalize this finding we have now studied large DNA fragments containing several adducts. The stability of the adducts within single-stranded DNA is demonstrated by absorption spectrophotometry and by replication mapping experiments. Several approaches are used to prove the lability of the adducts within double-stranded DNA. Replication mapping experiments reveal that an unmodified single-stranded DNA when mixed with double-stranded DNA modified by the platinum-triamine complex behaves as a single-stranded DNA modified by the triamine complex. After double-stranded DNA is modified by the platinum-triamine complex, intrastrand and interstrand cross-links are progressively formed during subsequent incubation as revealed by transcription mapping experiments and gel electrophoresis under denaturing conditions. Finally, replication mapping experiments show that the lability of the adducts within a double-stranded DNA depends upon the nature of the flanking nucleotide residues. All these results support the proposal that the DNA double helix acts as a catalyst in the reaction between DNA, cis-diamminedichloroplatinum(II) and N-methyl-2,7-diazapyrenium.

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Selected References

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  1. Axelrod V. D., Kramer F. R. Transcription from bacteriophage T7 and SP6 RNA polymerase promoters in the presence of 3'-deoxyribonucleoside 5'-triphosphate chain terminators. Biochemistry. 1985 Oct 8;24(21):5716–5723. doi: 10.1021/bi00342a005. [DOI] [PubMed] [Google Scholar]
  2. Comess K. M., Burstyn J. N., Essigmann J. M., Lippard S. J. Replication inhibition and translesion synthesis on templates containing site-specifically placed cis-diamminedichloroplatinum(II) DNA adducts. Biochemistry. 1992 Apr 28;31(16):3975–3990. doi: 10.1021/bi00131a013. [DOI] [PubMed] [Google Scholar]
  3. Comess K. M., Costello C. E., Lippard S. J. Identification and characterization of a novel linkage isomerization in the reaction of trans-diamminedichloroplatinum(II) with 5'-d(TCTACGCGTTCT). Biochemistry. 1990 Feb 27;29(8):2102–2110. doi: 10.1021/bi00460a020. [DOI] [PubMed] [Google Scholar]
  4. Corda Y., Job C., Anin M. F., Leng M., Job D. 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. 1991 Jan 8;30(1):222–230. doi: 10.1021/bi00215a032. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Gaucheron F., Malinge J. M., Blacker A. J., Lehn J. M., Leng M. Possible catalytic activity of DNA in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) and the intercalator N-methyl-2,7-diazapyrenium. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3516–3519. doi: 10.1073/pnas.88.9.3516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hollis L. S., Amundsen A. R., Stern E. W. 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. 1989 Jan;32(1):128–136. doi: 10.1021/jm00121a024. [DOI] [PubMed] [Google Scholar]
  8. Hollis L. S., Sundquist W. I., Burstyn J. N., Heiger-Bernays W. J., Bellon S. F., Ahmed K. J., Amundsen A. R., Stern E. W., Lippard S. J. Mechanistic studies of a novel class of trisubstituted platinum(II) antitumor agents. Cancer Res. 1991 Apr 1;51(7):1866–1875. [PubMed] [Google Scholar]
  9. Lemaire M. A., Schwartz A., Rahmouni A. R., Leng M. Interstrand cross-links are preferentially formed at the d(GC) sites in the reaction between cis-diamminedichloroplatinum (II) and DNA. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1982–1985. doi: 10.1073/pnas.88.5.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Malinge J. M., Sip M., Blacker A. J., Lehn J. M., Leng M. Formation of a DNA monofunctional cis-platinum adduct cross-linking the intercalating drug N-methyl-2,7-diazapyrenium. Nucleic Acids Res. 1990 Jul 11;18(13):3887–3891. doi: 10.1093/nar/18.13.3887. [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. Pinto A. L., Lippard S. J. Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum (II). Proc Natl Acad Sci U S A. 1985 Jul;82(14):4616–4619. doi: 10.1073/pnas.82.14.4616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Waring M. J. DNA modification and cancer. Annu Rev Biochem. 1981;50:159–192. doi: 10.1146/annurev.bi.50.070181.001111. [DOI] [PubMed] [Google Scholar]

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