Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

  • R. C. Rietbroek
  • P. J. M. van de Vaart
  • J. Haveman
  • F. A. Blommaert
  • A. Geerdink
  • P. J. M. Bakker
  • C. H. N. Veenhof
Original Paper Experimental Oncology


The cytotoxicity of cisplatin and cisplatin-DNA adduct formation in vitro and in vivo is clearly enhanced by hyperthermia. We investigated whether cytotoxicity and platinum-DNA adduct formation of two promising new third-generation platinum derivatives, lobaplatin [1,2-diamminomethylcyclobutane platinum(II) lactate] and oxaliplatin [oxalato-1,2-diaminocyclohexane platinum(II)], are also enhanced by hyperthermia. Cisplatin was used for comparison. SW 1573 cells were incubated with cisplatin, lobaplatin or oxaliplatin at different concentrations for 1 h at 37°, 41° and 43°C. The reproductive capacity of cells was determined by cloning experiments. Immunocytochemical detection of platinum-DNA adducts was performed with the rabbit antiserum NKI-A59. At 37°C, cisplatin was the most cytotoxic, followed by oxaliplatin and lobaplatin. Hyperthermia clearly enhanced the cytotoxicity of cisplatin, lobaplatin and oxaliplatin. There was no further increase in cytotoxicity at 43°C compared to 41°C for cisplatin and oxaliplatin. A further increase in cytotoxicity at 43°C was observed for lobaplatin. At 43°C thermal enhancement was higher for lobaplatin than for oxaliplatin, with the reverse pattern at 41°C. For both drugs, thermal enhancement of cytotoxicity was lower than observed for cisplatin. Immunocytochemical detection of platinum-DNA adducts was feasible for all the drugs. Adduct formation was enhanced at 43°C for cisplatin, lobaplatin and oxaliplatin with a relative increase of 410%, 170% and 180%. These results seem to confirm that an increase in platinum-DNA adduct formation is involved in the in vitro thermal enhancement of cytotoxicity. The observed thermal enhancement of cytotoxicity of lobaplatin and oxaliplatin in vitro warrants further in vivo investigations.

Key words

Hyperthermia induced Lobaplatin Oxaliplatin Cisplatin Platinum-DNA adduct formation Cytotoxicity 



thermal enhancement ratio


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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • R. C. Rietbroek
    • 1
  • P. J. M. van de Vaart
    • 3
  • J. Haveman
    • 2
  • F. A. Blommaert
    • 3
  • A. Geerdink
    • 2
  • P. J. M. Bakker
    • 1
  • C. H. N. Veenhof
    • 1
  1. 1.Department of Medical Oncology, F4-224Academic Medical CentreAmsterdamThe Netherlands
  2. 2.Department of Radiotherapy, University of AmsterdamAcademic Medical CentreAmsterdamThe Netherlands
  3. 3.The Netherlands Cancer InstituteAmsterdamThe Netherlands

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