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British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Jun;67(6):1285–1292. doi: 10.1038/bjc.1993.239

A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.

Y Fujiwara 1, M Nakamura 1, S Yokoo 1
PMCID: PMC1968491  PMID: 8512813

Abstract

Interstrand cross-linking, repair and lethal effects of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) (DWA2114R) were studied in normal human. Fanconi's anaemia (FA) and xeroderma pigmentosum group A (XPA) cells. Interstrand crosslinking by DWA2114R was slower than that by cisplatin (CDDP), since DWA2114R produced mainly Pt(II)-monoadducts after 1 h treatment, followed by progressive interstrand crosslinking to a maximum 5 h post-incubation, while CDDP induced rapidly interstrand crosslinks in approximately 70% DNA during the 1 h treatment, followed by a approximately 30% residual increase. At the maximum rate, DWA2114R was 18 times less interstrand-crosslinking than CDDP on the 1 mM basis. FA cells were specifically defective in the first half-excision of DWA2114R and CDDP-induced Pt(II) interstrand crosslinks, but XPA cells were as proficient as normal cells (t1/2 = 5-7 h). On the contrary, XPA cells were deficient in excision repair of intrastrand crosslinks, but FA cells were normal. In clonogenic survival curves of all types of cells, mean lethal doses (Do) of DWA2114R were an order of magnitude greater than those of CDDP. FA cells were most (3.5 times) sensitive (Do = 25.1 +/- 0.96 microM) and XPA cells were 1.9 times more sensitive (Do = 47.1 +/- 0.17 microM) to DWA2114R than normal cells (Do = 87.6 +/- 5.65 microM). DWA2114R and carboplatin with a cyclobutanedicarboxylato group exhibited almost similar lethal effects on each of normal, FA and XPA strains. FA (Do = 3.44 +/- 0.44 microM) and XPA cells (Do = 3.84 +/- 0.17 microM) were similarly 3-fold more sensitive to CDDP than normal (Do = 9.97 +/- 0.15 microM). On the basis of a single lethal hit (Do), thus DWA2114R and carboplatin effectively killed more FA cells defective in interstrand crosslink repair than XPA cells defective in intrastrand crosslink repair.

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Selected References

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  1. Akamatsu K., Endo K., Matsumoto T., Morikawa K., Koizumi M., Koizumi K., Mitsui H. Toxicological and tumoricidal evaluations of a new platinum complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato+ ++)platinum( II) monohydrate, in rats. Jpn J Cancer Res. 1991 Jun;82(6):724–731. doi: 10.1111/j.1349-7006.1991.tb01909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bedford P., Fichtinger-Schepman A. M., Shellard S. A., Walker M. C., Masters J. R., Hill B. T. Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines. Cancer Res. 1988 Jun 1;48(11):3019–3024. [PubMed] [Google Scholar]
  3. Ciccarelli R. B., Solomon M. J., Varshavsky A., Lippard S. J. In vivo effects of cis- and trans-diamminedichloroplatinum(II) on SV40 chromosomes: differential repair, DNA-protein cross-linking, and inhibition of replication. Biochemistry. 1985 Dec 17;24(26):7533–7540. doi: 10.1021/bi00347a005. [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. Interstrand cross-links and sequence specificity in the reaction of cis-dichloro(ethylenediamine)platinum(II) with DNA. Biochemistry. 1985 Sep 10;24(19):5027–5032. doi: 10.1021/bi00340a011. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Endoh K., Akamatsu K., Matsumoto T., Morikawa K., Honda M., Mitsui H., Koizumi M., Koizumi K., Matsuno T. Antitumor activity of a new platinum complex, 2-aminomethyl-pyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II). Anticancer Res. 1989 Jul-Aug;9(4):987–991. [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. Foster B. J., Harding B. J., Wolpert-DeFilippes M. K., Rubinstein L. Y., Clagett-Carr K., Leyland-Jones B. A strategy for the development of two clinically active cisplatin analogs: CBDCA and CHIP. Cancer Chemother Pharmacol. 1990;25(6):395–404. doi: 10.1007/BF00686049. [DOI] [PubMed] [Google Scholar]
  10. Fujiwara Y. Clustered repair of excisable 4-nitroquinoline-1-oxide adducts in a larger fraction of genomic DNA of xeroderma pigmentosum complementation group C cells. Carcinogenesis. 1989 Oct;10(10):1777–1785. doi: 10.1093/carcin/10.10.1777. [DOI] [PubMed] [Google Scholar]
  11. Fujiwara Y. Defective repair of mitomycin C crosslinks in Fanconi's anemia and loss in confluent normal human and xeroderma pigmentosum cells. Biochim Biophys Acta. 1982 Dec 31;699(3):217–225. doi: 10.1016/0167-4781(82)90110-5. [DOI] [PubMed] [Google Scholar]
  12. Fujiwara Y., Matsumoto A., Ichihashi M., Satoh Y. Heritable disorders of DNA repair: xeroderma pigmentosum and Fanconi's anemia. Curr Probl Dermatol. 1987;17:182–198. doi: 10.1159/000413483. [DOI] [PubMed] [Google Scholar]
  13. Fujiwara Y., Tatsumi M. Cross-link repair in human cells and its possible defect in Fanconi's anemia cells. J Mol Biol. 1977 Jul 15;113(4):635–649. doi: 10.1016/0022-2836(77)90227-3. [DOI] [PubMed] [Google Scholar]
  14. Goldstein R. S., Mayor G. H. Minireview. The nephrotoxicity of cisplatin. Life Sci. 1983 Feb 14;32(7):685–690. doi: 10.1016/0024-3205(83)90299-0. [DOI] [PubMed] [Google Scholar]
  15. Heiger-Bernays W. J., Essigmann J. M., Lippard S. J. Effect of the antitumor drug cis-diamminedichloroplatinum(II) and related platinum complexes on eukaryotic DNA replication. Biochemistry. 1990 Sep 11;29(36):8461–8466. doi: 10.1021/bi00488a037. [DOI] [PubMed] [Google Scholar]
  16. Iwata M., Izuta S., Suzuki M., Kojima K., Furuhashi Y., Tomoda Y., Yoshida S. Sequence-dependent termination of mammalian DNA polymerase reaction by a new platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-plati num(II) monohydrate). Jpn J Cancer Res. 1991 Apr;82(4):433–439. doi: 10.1111/j.1349-7006.1991.tb01867.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jones J. C., Zhen W. P., Reed E., Parker R. J., Sancar A., Bohr V. A. Gene-specific formation and repair of cisplatin intrastrand adducts and interstrand cross-links in Chinese hamster ovary cells. J Biol Chem. 1991 Apr 15;266(11):7101–7107. [PubMed] [Google Scholar]
  18. Kano Y., Fujiwara Y. Roles of DNA interstrand crosslinking and its repair in the induction of sister-chromatid exchange and a higher induction in Fanconi's anemia cells. Mutat Res. 1981 May;81(3):365–375. doi: 10.1016/0027-5107(81)90123-8. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Matsumoto T., Endoh K., Akamatsu K., Kamisango K., Mitsui H., Koizumi K., Morikawa K., Koizumi M., Matsuno T. Comparison of the antitumour effects and nephrotoxicity-inducing activities of two new platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato+ ++)-platinum (II) monohydrate, and its enantiomeric isomer. Br J Cancer. 1991 Jul;64(1):41–46. doi: 10.1038/bjc.1991.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Morikawa K., Honda M., Endoh K., Matsumoto T., Akamatsu K., Mitsui H., Koizumi M. Synthesis of platinum complexes of 2-aminomethylpyrrolidine derivatives for use as carrier ligands and their antitumor activities. Chem Pharm Bull (Tokyo) 1990 Apr;38(4):930–935. doi: 10.1248/cpb.38.930. [DOI] [PubMed] [Google Scholar]
  23. Page J. D., Husain I., Sancar A., Chaney S. G. Effect of the diaminocyclohexane carrier ligand on platinum adduct formation, repair, and lethality. Biochemistry. 1990 Jan 30;29(4):1016–1024. doi: 10.1021/bi00456a026. [DOI] [PubMed] [Google Scholar]
  24. Plooy A. C., van Dijk M., Berends F., Lohman P. H. Formation and repair of DNA interstrand cross-links in relation to cytotoxicity and unscheduled DNA synthesis induced in control and mutant human cells treated with cis-diamminedichloroplatinum(II). Cancer Res. 1985 Sep;45(9):4178–4184. [PubMed] [Google Scholar]
  25. Roberts J. J., Friedlos F. Quantitative estimation of cisplatin-induced DNA interstrand cross-links and their repair in mammalian cells: relationship to toxicity. Pharmacol Ther. 1987;34(2):215–246. doi: 10.1016/0163-7258(87)90012-x. [DOI] [PubMed] [Google Scholar]
  26. Rosenberg B., VanCamp L., Trosko J. E., Mansour V. H. Platinum compounds: a new class of potent antitumour agents. Nature. 1969 Apr 26;222(5191):385–386. doi: 10.1038/222385a0. [DOI] [PubMed] [Google Scholar]
  27. Sorenson C. M., Eastman A. Mechanism of cis-diamminedichloroplatinum(II)-induced cytotoxicity: role of G2 arrest and DNA double-strand breaks. Cancer Res. 1988 Aug 15;48(16):4484–4488. [PubMed] [Google Scholar]
  28. Szymkowski D. E., Yarema K., Essigmann J. M., Lippard S. J., Wood R. D. An intrastrand d(GpG) platinum crosslink in duplex M13 DNA is refractory to repair by human cell extracts. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10772–10776. doi: 10.1073/pnas.89.22.10772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Von Hoff D. D., Schilsky R., Reichert C. M., Reddick R. L., Rozencweig M., Young R. C., Muggia F. M. Toxic effects of cis-dichlorodiammineplatinum(II) in man. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1527–1531. [PubMed] [Google Scholar]

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