Nitrosoureas Modes of Action and Perspectives in the Use of Hormone Receptor Affine Carrier Molecules

Authors

  • G. Eisenbrand Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • M. R. Berger Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • H. P. Brix Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • J. E. Fischer Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • K. Mühlbauer Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • M. R. Nowrousian Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • M. Przybilski Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • M. R. Schneider Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • W. Stahl Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • W. Tang The Department of Internal Medicine, West-German Tumor Center, Essen, The Department of Organic Chemistry, University of Mainz, Mainz
  • O. Zelezny Department of Food Chemistry and Environmental Toxicology, University of Kai-Serslautern, Kaiserslautern, The Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg
  • W. J. Zeller Department of Chemistry and Pharmacy, University of Regensburg, Regensburg, West Germany

DOI:

https://doi.org/10.3109/02841868909111248

Keywords:

Alkylating, cross-linking nitrosoureas, estradiol- linked, dihydrotestosterone-linked, CNC-amino acids, eroid es- te, mammary, prostatic cancer

Abstract

Mechanisms of DNA adduct formation by antineoplastic 2-chloroethyl-N-nitrosoureas (CNUs) and of DNA damage induced by these compounds are discussed. CNUs are alkylating agents that form DNA-DNA cross-links as well as 2-chloroethylated and 2-hydroxyethylated adducts, the N-7-position of guanine being the predominantly alkylated site. A close correlation exists between the potential of a given compound to induce DNA-DNA cross-links and its antineoplastic effectiveness. However, levels of DNA-DNA cross-linking in bone marrow and extent of myelosuppression as measured in rodents are also closely correlated. The design of new cross-linking analogues capable of directing the antineoplastically relevant activity predominantly to the target tumour appears therefore to be of great promise. Cross-linking agents have been attached to a variety of steroid hormone carrier molecules and the conjugates have been tested in structure-activity studies using hormone-receptor containing animal tumours. These studies have revealed that some hormone-linked antineoplastic agents are highly effective in receptor positive experimental tumours and are superior to mixtures of unlinked alkylating agents with hormones. Indications for a relative enrichment of DNA damaging effects in the tumour tissue and for reduced myelotoxicity have been obtained with specific hormone conjugates.

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Published

1989-01-01

How to Cite

Eisenbrand, G., Berger, M. R., Brix, H. P., Fischer, J. E., Mühlbauer, K., Nowrousian, M. R., … Zeller, W. J. (1989). Nitrosoureas Modes of Action and Perspectives in the Use of Hormone Receptor Affine Carrier Molecules. Acta Oncologica, 28(2), 203–211. https://doi.org/10.3109/02841868909111248

Issue

Vol. 28 No. 2 (1989): Acta Oncologica

Section

Articles