Harries, GC; Boobis, AR; Sesardic, D; Edwards, RJ; Davies, DS
The comparative activation of aromatic amines to mutagenic metabolites by human and rat liver was studied in-vitro. The ability of hepatic post mitochondrial supernatant, S9, to activate 2-aminofluorene (153786) (AF), 2-acetylaminofluorene (53963) (AAF), 3-amino-1-methyl-5H-pyrido(4,3-b)indole (62450071) (TrpP-2), 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (62450060) (TrpP-1), 2-amino-6-methyl-dipyrido(1,2-a:3',2'-d)imidazole (GluP-1), 2-amino-dipyrido(1,2-a:3',2'-d)imidazole (GluP-2), 2-amino-3-methylimidazo(4,5-f)quinoline (76180966) (IQ), and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) to mutagenic substances was evaluated using the Ames-Salmonella system. S9 was obtained from human livers and from control and Aroclor-1254 (11097691) treated rats. All compounds were potent mutagens. The S9 preparation from rats induced by Aroclor-1254 was most active in producing mutagenic metabolites of TrP-1, TrP-2, GluP-1, and GluP-2. Human liver S9 activated these compounds to an extent similar to that seen with S9 from control rats; it was most active in converting IQ, AF, and AAF to mutagens. MeIQ was the most mutagenic compound when incubated with Aroclor-1254 treated rat S9 or human S9. The authors suggest that more than one isozyme of cytochrome-P-450 is involved in the mutagenic activation of aromatic amines.