Abstract
Isoniazid showed mutagenic activity in submammalian test systems. If these results were also applicable to man, the mutational load of the population due to isoniazid would be rather large, because this is a widely used agent. We, therefore, carried out mutation experiments in mice, using two different test systems: the dominant lethal test and the host-mediated assay with Salmonella typhimurium G 46 as indicator organism. These methods were chosen because we intended to cover two different spectra of mutations: point mutations and dominant lethal mutations which are thought to be the result of chromosome aberrations.
Isoniazid was mutagenic in the host-mediated assay after a total dose of 25–150 mg/kg s. c., but did not induce dominant lethal mutations in mice.In vitro, isoniazid did not show mutagenic activity in this microbial strain, whereas hydrazine was strongly mutagenic in vitro as well as in vivo. The mutagenicity of isoniazid in the host-mediated assay may be explained by the formation of hydrazine in the mouse organism.
Although in the host-mediated assay the mammalian metabolism is taken into account, the mutations are induced in microorganisms. Thus we have only indications but no real proof that isoniazid is mutagenic in mammals. These findings do, however, call for profound and critical studies to elucidate the question of whether isoniazid could be mutagenic for man.
Zusammenfassung
Isoniazid erhöhte in der intra-animalen Kultur (host-mediated assay) mit Salmonella typhimurium G 46 als Indicatororganismus die Mutationsfrequenz, löste dagegen nach Applikation an männliche Mäuse keine dominanten Letalmutationen aus. In stärkerem Maß erzeugte Hydrazin Mutationen in der intra-animalen Kultur. Im host-mediated assay werden die Mutationen nur an Mikroorganismen induziert und nachgewiesen; der Befund kann aber nur Hinweis auf eine mögliche mutagene Wirkung am Menschen sein. Da die Substanz jedoch weiten Bevölkerungskreisen verabreicht wird, ist eine gründliche Untersuchung der mutagenen Eigenschaften des INH erforderlich.
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Vortrag gehalten bei der 25. Tagung der Deutschen Gesellschaft für Lungenkrankheiten und Tuberkulose, Hamburg, 20.–23. Sept. 1972.
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Kehler, E., Röhrborn, G., Propping, P. et al. Zur Mutagenität des INH. Pneumologie 148, 223–226 (1973). https://doi.org/10.1007/BF02114106
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DOI: https://doi.org/10.1007/BF02114106