Modulation of aromatic amine mutagenicity in Salmonella typhimurium with rat-liver 9000 g supernatant or monolayers of rat hepatocytes as an activation system.

摘要: Abstract 2-Aminofluorene (AF), 2-acetylaminofluorene (AAF) and N -hydroxy-2-acetylaminofluorene (N-OH-AAF) were studied for mutagenic activity in S. typhimurium either liver 9000 f supernatant fractions (S9) or monolayer cultures of hepatocytes isolated from Wistar rats used as an activation system. All 3 compounds converted into mutagens excreted the incubation medium by cell-culture system, with N-OH-AAF > AF AAF. Cultures 24 h after plating less efficient promutagen conversion than 2 h. Phenobarbital, but not 3-methylcholanthrene, pretreatment caused similar effects on AF, AAF mutagenicity both S9 hepatocyte cultures. The mutagenicities reduced cytochrome-P-450 inhibitors metyrapone α-naphthoflavone, whereas was increased using inhibitors. Further, microsomal deacetylase inhibitor paraoxon only a moderate reduction mutagenicity, total inhibition mutagenicity. No significant effect seen. With no ascorbate observed. In contrast, all when Incubation monolayers sulfate-free did change N-OH-AAF. Galactosamine, glucuronidation cells, addition cofactor however, had effect. A AAF, that N-OH-AAF, observed glutathione (GSH) systems. On other hand, cellular GSH depletion seen aromatic-amine data indicate culture system offers advantages over conventional liver-sub-fraction model, vivo, metabolism aromatic amine mutagens/carcinogens.