1,3-Dialkyltriazenes: Reactive Intermediates and DNA Alkylation

M. B. Kroeger-Koepke, R. H. Smith, E. A. Goodnow, J. Brashears, L. Kratz, A. W. Andrews, W. G. Alvord, C. J. Michejda

Research output: Contribution to journalArticle

Abstract

The reactions of calf thymus (ct) DNA with 1,3-dimethyltriazene (DMT), N-methyl-N-nitrosourea (MNU), 1,3-diethyltriazene (DET), N-ethyl-N-nitrosourea (ENU), and l-ethyl-3-methyltriazene (MET) were studied as a function of concentration of the alkylating agents, of various buffers, and of ionic strength. The amount of alkylation at the 7- and Oppositions of guanine increased linearly with dose over a 10-fold concentration range. The slopes of the DMT and MNU curves were identical as were those of DET and ENU. These data suggest that both types of compounds alkylate DNA via a similar intermediate, presumably the corresponding alkanediazonium ion. MET methylates and ethylates DNA, the amount of each product being a function of the competitive formation of the two diazonium ions possible from MET. The MET product ratios could be reproduced by an appropriate mixture of DET and DMT. The alkylation of DNA by DMT and by MET is very sensitive to ionic strength, to the nature of the buffer, and to the identity of the salt used to balance ionic strength. In general, the reaction is favored by low ionic strength, by amine rather than oxy acid buffers, and by doubly charged inert anions. The alkylation of DNA is inversely proportional to the logarithm of the ionic strength over a wide range. The mutagenic activity of triazenes in Salmonella typhimurium is correlated very well with the ability of the triazenes to form adducts, particularly O6-guanine adducts. Thus, symmetrical 1,3-dialkyltriazenes are mutagens in the order of methyl ≫ ethyl > butyl = isopropyl, and unsymmetrical l-alkyl-3-methyltriazenes are mutagens in the order ethyl > butyl > isopropyl. The latter order follows the rate of production of the methanediazonium ion, the most mutagenic of the diazonium ions.

Original languageEnglish (US)
Pages (from-to)334-340
Number of pages7
JournalChemical research in toxicology
Volume4
Issue number3
DOIs
StatePublished - May 1 1991
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of '1,3-Dialkyltriazenes: Reactive Intermediates and DNA Alkylation'. Together they form a unique fingerprint.

  • Cite this

    Kroeger-Koepke, M. B., Smith, R. H., Goodnow, E. A., Brashears, J., Kratz, L., Andrews, A. W., Alvord, W. G., & Michejda, C. J. (1991). 1,3-Dialkyltriazenes: Reactive Intermediates and DNA Alkylation. Chemical research in toxicology, 4(3), 334-340. https://doi.org/10.1021/tx00021a013