The biological activity of cisplatin and dibromodulcitol in combination therapy

A. Jeney, I. Kovalszky, E. Rásó, R. E. Durand, J. Furesz, K. Lapis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival time in mice bearing P388 solid lymphomas than either of the drugs alone. In the human metastatic melanoma HT-168 xenograft model the combined application of DBD and CDDP was also very effective, inducing a reduction in the number and volume of metastatic nodules. For V79 spheroids, DBD was mainly cytotoxic against the internal, quiescent cells, whereas cisplatin primarily killed cells in the proliferating, external regions of the spheroids. When combined, the drugs appeared to act synergistically throughout the spheroids. Studies on plasmid DNA showed that CDDP primarily generates cross-links, whereas single-strand breaks were dominant after DBD treatment. Upon using an assay for cleavage by restriction nuclease, antagonistic action of DBD and CDDP in combination may occur, nevertheless more strand breaks were always observed in these samples. These results suggest that the efficacy of combined DBD and CDDP is in part a result of 'spatial cooperation' by the drugs (i.e. affecting different cells) and in part the result of DNA damage produced by the combination treatments.

Original languageEnglish
Pages (from-to)317-321
Number of pages5
JournalBritish Journal of Cancer
Volume71
Issue number2
Publication statusPublished - 1995

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Mitolactol
Cisplatin
Therapeutics
Pharmaceutical Preparations
Heterografts
DNA Damage
Melanoma
Lymphoma
Plasmids
Survival
DNA

Keywords

  • Cisplatin
  • Dibromodulcitol
  • DNA damage
  • Spheroids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The biological activity of cisplatin and dibromodulcitol in combination therapy. / Jeney, A.; Kovalszky, I.; Rásó, E.; Durand, R. E.; Furesz, J.; Lapis, K.

In: British Journal of Cancer, Vol. 71, No. 2, 1995, p. 317-321.

Research output: Contribution to journalArticle

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