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Structural Modifications and Repair of DNA in Neuro-Oncogenesis by N-Ethyl-N-nitrosourea

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Book cover Modified Nucleosides and Cancer

Abstract

Structural alterations of DNA in the chromatin of target cells are primary events in the multistep process of malignant transformation and tumorigenesis by most chemical carcinogens (Lawley 1976; Pegg 1977; Weinstein 1977; Grover 1979; Singer 1979; Pullman et al. 1980; Rajewsky 1980a). In general, covalent binding occurs between nucleophilic centers (electron-rich nitrogen and oxygen atoms) in cellular DNA and highly reactive, electrophilic derivatives (ultimate carcinogens) generated from the respective parent compounds (precarcinogens), either by enzyme-catalyzed “metabolic activation” or via nonenzymatic decomposition (Miller and Miller 1976, 1979). As a consequence of their reaction with DNA, most chemical carcinogens are also mutagenic (McCann et al. 1975; Nagao et al. 1978; Hollstein et al. 1979). The strong correlation of carcinogenicity and mutagenicity does not, however, constitute proof for an obligatory requirement of mutation (nor even of modification of DNA structure in general) for malignant tranformation. Cellular macromolecules other than DNA also contain multiple nucleophilic sites which can, and indeed do, react with carcinogen-generated electrophiles. In spite of this proviso, the central importance of DNA structure and conformation for the expression of genetic information provides a strong argument for a critical role of DNA alterations as a prerequisite for the initiation of carcinogenesis by chemical agents.

Experimental studies in the author’s laboratory were supported by the Deutsche Forschungsgemeinschaft (SFB 102) and by the Fritz Thyssen Stiftung (1980/2/41)

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  1. Institut für Zellbiologie (Tumorforschung), Universität Essen (GH), Hufelandstrasse 55, 4300, Essen 1, Germany

    M. F. Rajewsky

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  1. Zentrallaboratorium für Mutagenitätsprüfung, Deutschen Forschungsgemeinschaft, Breisacher Strasse 33, D-7800, Freiburg, Germany

    Gisela Nass

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Rajewsky, M.F. (1983). Structural Modifications and Repair of DNA in Neuro-Oncogenesis by N-Ethyl-N-nitrosourea. In: Nass, G. (eds) Modified Nucleosides and Cancer. Recent Results in Cancer Research/Fortschritte der Krebsforschung/Progrès dans les recherches sur Ie cancer, vol 84. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81947-6_4

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