Journal of Cancer Research and Clinical Oncology

, Volume 126, Issue 4, pp 198–204

Differential modulation of chemosensitivity to alkylating agents and platinum compounds by DNA repair modulators in human lung cancer cell lines

  • M. M. Heim
  • W. Eberhardt
  • S. Seeber
  • M. R. Müller
ORIGINAL PAPER

DOI: 10.1007/s004320050033

Cite this article as:
Heim, M., Eberhardt, W., Seeber, S. et al. J Cancer Res Clin Oncol (2000) 126: 198. doi:10.1007/s004320050033

Abstract

Purpose: Modulation of DNA repair represents one strategy to overcome cellular drug resistance to alkylating agents and platinum compounds. The effects of different known DNA repair modulators such as O6-benzylguanine (6 μg/ml), fludarabine (25 ng/ml), aphidicolin (8.5 ng/ml), pentoxifylline (1.4 μg/ml) and methoxamine (12.4 μg/ml) on the cytotoxicity of mafosfamide, chlorambucil, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin and carboplatin were tested in human lung cancer cell lines. Methods: Chemosensitivity of the human adenocarcinoma cell line MOR/P and the cisplatin-resistant subline MOR/CPR as well as the large-cell lung cancer cell line L23/P and its cisplatin-resistant counterpart L23/CPR were evaluated by the MTT colorimetric assay. Results:O6-benzylguanine, an inhibitor of O6-alkylguanine-DNA alkyltransferase, significantly sensitised MOR/P and MOR/CPR cells to the cytotoxic effect of BCNU. Fludarabine, methoxamine and aphidicolin did not change the chemosensitivity of the parental and cisplatin-resistant cell lines to any cytotoxic drug tested. Interestingly, O6-benzylguanine enhanced the chemoresistance of parental and cisplatin-resistant cell lines to platinum compounds. Also, pentoxifylline increased resistance of the MOR cell lines to mafosfamide. Conclusions: Modulation of DNA repair elicits not only chemosensitisation but may also enhance cellular resistance to DNA-affine drugs.

Key words DNA repair Resistance modifier Drug resistance 

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • M. M. Heim
    • 1
  • W. Eberhardt
    • 1
  • S. Seeber
    • 1
  • M. R. Müller
    • 1
  1. 1.Department of Internal Medicine (Cancer Research), University of Essen Medical School, West German Cancer Centre Essen, Hufelandstr 55, D-45122 Essen, Germany e-mail: m.r.mueller@uni-essen.de Tel.: +49-201-723 3155 Fax: +49-201-723 5924DE

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