DNA damage and repair induced by diazoacetyl derivatives of amino acids with different mechanism of cytotoxicity. Correlations with mutagenicity and carcinogenicity

G. Brambilla, M. Cavanna, P. Carlo, R. Finollo, L. Sciaba, S. Parodi, C. Bolognesi

Research output: Contribution to journalArticle

Abstract

Eight synthetic N-diazoacetyl amino acids, prepared by inserting a diazoacetyl group onto the α-nitrogen of a natural amino acid, and two natural diazoazetyl amino acids, azaserine (O-diazoacetyl-L-serine) and DON (6-diazo-5-oxo-L-norleucine), have been studied by autoradiography for their capacity to induce DNA repair synthesis in mouse cells cultivated "in vitro". Dose-dependent unscheduled DNA synthesis was present in cells treated with the eight N-diazoacetyl derivatives, and was absent in cells exposed to approximately equitoxic concentrations of azaserine and DON. Azaserine and DON, unlike N-diazoacetyl derivatives, did not alkylate γ-(4-nitrobenzyl) pyridine at an appreciable extent. When DNA damage (single stranded breaks or weak points in alkali) was measured by the sensitive technique of alkaline elution, DGA was found about 4 times as potent as azaserine and about 12 times as DON on a molar basis, but about 800 and 17,000 times as potent as azaserine and DON respectively by extrapolating to equitoxic concentrations. Carcinogenicity and mutagenicity seem to follow mainly the capability of inducing DNA damage.

Original languageEnglish
Pages (from-to)7-20
Number of pages14
JournalJournal of Cancer Research and Clinical Oncology
Volume94
Issue number1
DOIs
Publication statusPublished - Jan 1979

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Keywords

  • Carcinogenicity
  • Diazoacetyl amino acids
  • DNA damage
  • DNA repair

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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