Testing of Drugs for Combined Mutagenesis with Sodium Nitrite in the Host-mediated Assay
Mutagenic activity of the drugs analgine and aminophenazone was tested in the intraperitoneal and intrasanguine host-mediated assay after oral application together with equimolar doses of sodium nitrite. Salmonella typhimurium strain G46 was used as genetic indicator system; mice served as host animals for the bacteria. Analgine was found to be weakly mutagenic in the dose 2 mM/kg together with nitrite, aminophenazone was a strong mutagen in combination with nitrite in the doses 2 mM/kg and 0.2 mM/kg using the intrasanguine test with 1 h incubation of bacteria in the liver. In the intraperitoneal variant with 3 h incubation time of bacteria only aminophenazone was slightly mutagenic at the highest dose tested, 2 mM/kg. The relative nitrosation rate for aminophenazone was calculated by means of regression lines for mutagenic activity of dimethylnitrosamine and was found to be in the range of 2% in both systems for a dose of 2 mM/kg precursors.
Key wordsHost-mediated assay Aminophenazone Analgine Sodium nitrite Nitrosation Dimethylnitrosamine Nitroso compounds In vivo formation
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