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Factors Influencing the Formation and Persistence of Platinum-DNA Adducts in Tissues of Rats Treated with Cisplatin

  • C. L. Litterst
  • M. C. Poirier
  • E. Reed
Part of the Developments in Oncology book series (DION, volume 53)

Abstract

The importance of cisplatin as a cancer chemotherapeutic agent has become increasingly obvious during the past 10–15 years. Studies of the mechanism of action of this compound predate clinical studies and established very early that the antitumor effect of cisPt was due to its ability to inhibit DNA synthesis. Further studies established the probability that DNA inhibition was caused by formation of a bidentate link between the de-chlorinated cisPt molecule and nucleophilic sites on the DNA strand, likely to be either N7 or 06 of the guanine base. Recent studies by several groups (1–3) have shown that the platinum-DNA linkage is predominantly between two guanine bases (G-G) and between adenine and guanine (A-G) on the same DNA strand (intrastrand cross link) and these intrastrand links correlate closely with antitumor efficacy and DNA inhibition.

Keywords

Adduct Formation Adduct Level Guanine Base Total Platinum Male Kidney 
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.
    Poirier MC, SJ Lippard, LA Zwelling, HM Ushay, D Kerrigan, CC Thill, SM Santela, D Grunberger, SH Yuspa (1982), Proc. Nat. Acad. Sci.79:6443–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Plooy, ACM, AMJ Fichtinger-Shepman, HH Schutte, M van Dijk, PHM Lohman (1985), Carcinogenesis 6:561–566.PubMedCrossRefGoogle Scholar
  3. 3.
    Lippard, SJ, HM Ushay, CM Merkel, MC Poirier (1983) Biochem. 22: 5165–68.CrossRefGoogle Scholar
  4. 4.
    Litterst, CL, In: Biochemical Mechanisms of Platinum Antitumour Drugs (DCH McBrien & TF Slater, eds) IRL Press, Oxford, 1986, pp 227–254.Google Scholar
  5. 5.
    Levi, J, C Jacobs, S Kaiman, M McTigue, M Winer (1980), J. Pharmacol. exptl. Therapeut. 213:545–550.Google Scholar
  6. 6.
    Uozumi, J & CL Litterst, (1985) Cancer Chemother Pharmacol 15:93–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Aull, JL, RL Allen, AR Bapat, HH Daron, ME Friedman, JF Wilson (1979) Biochem Biophys Acta 571:352–358.PubMedGoogle Scholar
  8. 8.
    Saferstein, R, P Miller, S Dikman, N Lyman & C Shapiro (1981), Am J Physiol 41:F175–179.Google Scholar
  9. 9.
    Guiguet, M, J-J Kupiec, A-J Valleran, In: Cell Cycle Clocks (LN Edmunds, ed) M. Dekker, NY 1984, pp 97–111.Google Scholar
  10. 10.
    Farber, E & DSR Sarma (1987) Lab. Invest. 56:4–22.PubMedGoogle Scholar
  11. 11.
    Ellman, GL (1959) Arch Biochem Biophys 82:70–77.PubMedCrossRefGoogle Scholar
  12. 12.
    Osman, N & CL Litterst (1983), Cancer Lett 19:107–111.PubMedCrossRefGoogle Scholar
  13. 13.
    Litterst, CL & VG Schweitzer (1984) Cancer Chemother Pharmacol 12: 12:46–49.PubMedGoogle Scholar
  14. 14.
    Reed, E, CL Litterst, C Thill, S Yuspa, & M Poirier (1987) Cancer Res 47:718–722.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1988

Authors and Affiliations

  • C. L. Litterst
  • M. C. Poirier
  • E. Reed

There are no affiliations available

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