Zusammenfassung
Monohalogenierte Methane können mutagen und karzinogen wirken. Die vorliegende Arbeit wurde durchgeführt, um den diesen Winkungen möglicherweise zugrundeliegenden Mechanismus, nämlich die Methrylierung von DNA, zu untersuchen. Hierzu wurden die DNA-Addukte aus Organen von gegenüber14C-markierten Methylnalogeniden exponierten F-344 Ratten mit Hilfe von Hochleistungsflüssigkeitschromatographie (HPLC) und Gaschromatographie gekoppelt mit Massenspek trometrie(GC/MS) getrennt und identifiziert. Folgende Ergebnisse konnten erzielt werden: Die Trennung von enzymatisch nydrolisierten DNA-Proben aus Organen von Ratten, die oral und innalativ gegen14C-Methylbromid und14C-Methyliodid exponiert worden waren, über HPLC und die Bestimmung der Radioaktivitätsverteilung in den Fraktionen ergab neben einem Einbau von14C in die physiologischen Basen die Bildung von DNA-Addukten, nämlich 7-Methylguanin (7-MeG) und O6-Methyldesoxyguanosin (O6-MedG). Die Bildung dieser DNA-Addukte war von Organ zu Organ nur quantitativ unterschiedlich. Die Trennung von entsprechenden sauer hydrolisierten DNA-Proben nach Zusatz von internem Standard (6-MeG) über HPLC konnte Bildung von O6-MeG bestätigen.14C-7-MeG und14C-3-Methyladenin (14C-3-MeA) konnten mit GC/MS Analyse identifiziert werden.
Abstract
Monohalogenated methanes (methyl chloride, methyl bromide and methyl iodide) are mutagenic and carcinogenic. The possible mechanism of these effects, DNA methylation, was studied. DNA adducts from orgnas of F344 rats exposed to these chemicals were separated and identified with high performance liquid chromatography (HPLC) and gaschro-matography/massspectrometry (GC/ MS). DNA adducts, 7-methylguanine (7-MeG) and O6-Methylguanine(08-MeG), incorporation of14C into de novo synthesis of nucleobases could be observed in enzymatic DNA hydrolysates by HPLC and determination of the radioactivity in the fractions. The formation of DNA add,ue,ts in the studied organs was only quantitatively different. The formation of O6-MeG was further pioved by analysing the acidic hydrolysates using HPLC with non-radioactive O6MeG as internal standard. 7-MeG and 3-MeA were identified with GC/MS analysis.
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Diese Arbeit wurde im Institut für Arbeitsphysiologie an der Universität Dortmund durchgeführt.
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Dai-gen, X., Han-zhen, H., Guo-gao, Z. et al. DNA-Methylierung von monohalogenierten Methanen in F-344 Ratten. Journal of Tongji Medical University 13, 100–104 (1993). https://doi.org/10.1007/BF02887924
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DOI: https://doi.org/10.1007/BF02887924