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Metabolism of nitrosamines in vivo

II. On the Methylation of nucleic acids by aliphatic di-n-Alkyi-nitrosamines in vivo, caused by β-oxydation: the increased formation of 7-methyl-guanine after application of β-hydroxypropyl-propyl-nitrosamine compared to that after application of di-n-propyl-nitrosamine

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Summary

The synthesis of 1-(14C)- and 2-(14C)-β-hydroxypropyl-propyl-nitrosamine was described. Administration of the compounds to rats led to the formation of labelled 7-methyl-guanine in the RNA and DNA of liver only when the 1-(14C)-labelled compound was injected. The amount of (14C)-labelled 7-methyl-guanine was 50 times higher than that found after administration of 1-(14C)-di-n-propyl-nitrosamine. These data support the hypothesis that di-n-alkyl-nitrosamines with more than two carbon atoms per alkyl group are degraded to methylating agents by β-hydroxylation.

In contrast to the application of di-n-alkyl-nitrosamines not hydroxylated in the β-position, no other labelled alkylated base than 7-methyl-guanine was found.

Zusammenfassung

Die Synthese von 1-(14C)- und 2-(14C)-β-Hydroxypropyl-propyl-nitrosamin wurde beschrieben. Nur nach Applikation von der in 1-Stellung 14C-markierten Verbindung ließ sich in den Nucleinsäuren der Rattenleber 7-(14C)-Methylguanin nachweisen. Die Menge an 7-(14C)-Methylguanin betrug etwa das 50 fache derjenigen, die nach Applikation äquimolarer Mengen di-n-Propyl-nitrosamin gefunden wurde. Durch dieses Ergebnis wird die Hypothese erhärtet, daß di-n-Alkyl-nitrosamine mit mehr als 2 C-Atomen pro Alkylgruppe durch β-Oxidation in vivo zu methylierenden Verbindungen abgebaut werden. Außer 7-Mehylguanin ließ sich keine markierte Base nachweisen. Dies zeigt, daß im Gegensatz zu anderen di-n-Alkylnitrosaminen eine in β-Stellung hydroxylierte Seitenkette in vivo nicht auf die Nucleinsäure übertragen wird.

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Authors and Affiliations

  1. Institut für experimentelle Toxikologie und Chemotherapie Am Deutschen Krebsforschungszentrum, Heidelberg

    F. W. Krüger

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  1. F. W. Krüger
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This work was supported by the „Fonds der Chemischen Industrie“. I thank Mr. H. Braun, Mrs. J. Knauft, Mss. G. Steuer and Mr. H. Stutz for their invaluable assistance and Dr. J. Althoff for his help in the preparation of the English manuscript.

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Krüger, F.W. Metabolism of nitrosamines in vivo . Z. Krebsforsch. 79, 90–97 (1973). https://doi.org/10.1007/BF00284383

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