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Experimental Studies with Methylhydrazine Derivatives

Published online by Cambridge University Press:  01 August 2014

W. Bollag
W. Bollag*
Affiliation:
Hoffmann La Roche, Basel

Summary

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Natulan (Procarbazine) is a methylhydrazine derivative which in animal experiments inhibits a series of transplantable tumours. The Walker carcinoma is markedly affected. Even well established Walker tumours disappear completely under Natulan treatment. Tumour tissue is replaced by fibrous tissue. Natulan does not act selectively on neoplastic tissue, it also depresses the growth of other rapidly proliferating tissues such as the bone marrow.

As regards the mechanism of action the following data are known: Natulan lowers the mitotic index by prolonging the interphase and hindering the cell from entering into mitosis. In Ehrlich ascites tumour cells chromatid breaks were observed. Natulan depolymerizes deoxyribonucleic acid (DNA) in vitro. In vivo the synthesis of DNA is inhibited. Furthermore alkylation of purine bases has been demonstrated. All these mechanisms may be responsible for the cytotoxic effect of methylhydrazine derivatives. Natulan does not possess cross-resistance towards other cytotoxic agents. This phenomenon is a further proof of its particular mechanism of action.

Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 17 , Issue 1 , January 1968 , pp. 158 - 170
Copyright
Copyright © The International Society for Twin Studies 1968

References

Berneis, K. et al. (1963). Der pro-oxydative Effekt tumorhemmender Methylhydrazin-Verbindungen. Helv. Chim. Acta, 46: 2157–2167.CrossRefGoogle Scholar
Berneis, K. et al. (1963). The degradation of deoxyribonucleic acid by new tumor inhibiting compounds: the intermediate formation of hydrogen peroxide. Experientia, 19: 132–133.CrossRefGoogle ScholarPubMed
Berneis, K. et al. (1964). Die Auslösung von Fenton-Reaktionen durch cytotoxische Methylhydrazin-Verbindungen. Helv. Chim. Acta, 47: 1903–1911.CrossRefGoogle Scholar
Bollag, W. (1963). The tumor-inhibitory effects of the methylhydrazine derivative Ro 4-6467/1 (NSG-77213). Cancer Chemother. Rep., 33: 1–4.Google Scholar
Bollag, W. (1964). Investigations with methylhydrazine derivatives. In: Chemotherapy of Cancer. Ed. Plattner. Elsevier, Amsterdam, London, New York, 191–197.Google Scholar
Bollag, W. Grunberg, E. (1963). Tumor inhibitory effects of a new class of cytotoxic agents: methylhydrazine derivatives. Experientia, 19: 130–131.CrossRefGoogle ScholarPubMed
Bollag, W. Theiss, E. (1964). Selective toxicity of antitumor agents: methylhydrazine derivatives. In: Chemotherapy of Cancer. Ed. Plattner, . Elsevier, Amsterdam, London, New York, 311–313.Google Scholar
Brookes, P. (1965). Studies on the mode of action of ibenzmethyzine. In: Natulan. Ed. Jelliffe, and Marks, . Wright & Sons, Bristol, 9–12.Google Scholar
Fölsch, E. et al. (1964). Über die Wirkung eines neuen Cytostaticums (Ro 4-6467) auf den Einbau markierten Glycins in Tumorzellen. Verh. Deutsch. Ges. Inn. Med., 70: 995–998.Google Scholar
Koblet, H. Personal Communication.Google Scholar
Kreis, W. et al. (1966). Studies on the metabolic fate of the C14-labelled methyl group of a methylhydrazine derivative in P 815 mouse leukemia. Experientia, 22: 431–433.CrossRefGoogle Scholar
Mosimann, W. Personal Communication.Google Scholar
Obrecht, P. et al. (1964). Zur Frage der biochemischen Wirkung eines neuen Cytostaticums, Ro 4-6467, aus der Klasse der Methylhydrazinderivate. Chemotherapia, 8: 106–113.CrossRefGoogle Scholar
Rutishauser, A. Personal Communication.Google Scholar
Rutishauser, A. Bollag, W. (1963). Cytological investigations with a new class of cytotoxic agents: methylhydrazine derivatives. Experientia, 19: 131–132.CrossRefGoogle ScholarPubMed
Rutishauser, A. Bollag, W. (1967). Untersuchungen über den Wirkungsmechanismus von Procarbazin (Natulan). Experientia, 23: 222–223.CrossRefGoogle ScholarPubMed
Staiger, G. R. Personal Communication.Google Scholar
Trepel, F. et al. (1966). Nukleinsäuresynthese und Zytostaticawirkung in pathologischen Lymphknotenzellen. Med. Klin., 61: 618–622.Google Scholar
Weitzel, G. Personal Communication.Google Scholar
Weitzel, G. et al. (1964). Cytostatischer Wirkungsmechanismus der Methylhydrazine. Experientia, 20: 38–39.CrossRefGoogle ScholarPubMed
Zeller, P. et al. (1963). Methylhydrazine derivatives, a new class of cytotoxic agents. Experientia, 19: 129.CrossRefGoogle ScholarPubMed