Metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline IQ and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in suspensions of isolated rat-liver cells.
Suspensions of rat-liver cells metabolized (14)C-labelled 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) to metabolites that were ethyl acetate extractable, water soluble or covalently bound to macromolecules. The major ethyl acetate extractable metabolite(s) had a retention time on the high-performance liquid chromatograph (HPLC), an ultraviolet spectrum and an R(f) value on the thin-layer chromatograph that corresponded to those of the N-acetylated derivative. Relatively more of this metabolite was formed from MeIQ than from IQ. In contrast, IQ was more easily converted to water-soluble metabolites than was MeIQ. The amount of covalently bound metabolite(s) found with MeIQ as test substance was larger than that found with IQ. No major increase in the ethyl acetate-extractable metabolites was obtained after incubation of the aqueous phase with beta-glucuronidase or aryl sulphatase in comparison with untreated controls. HPLC analysis showed that after acid hydrolysis of the water-soluble metabolites, about 55 and 20% of the hydrolysed metabolites had retention times that were the same as those of IQ and MeIQ, respectively. The ratio between covalently bound (activated) metabolites and water-soluble (detoxified) metabolites was larger for MeIQ than for IQ. From these data, one would expect MeIQ to be more potent than IQ as a liver carcinogen in male rats.
Holme
J A
JA
Department of Toxicology, National Institute of Public Health, Geitmyrsveien 75, N-0462 Oslo 4, Norway.
Alexander
J
J
Becher
G
G
Trygg
B
B