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Genotoxic activity of the N-acetylated metabolites of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ)

Brunborg, G.; Holme, J.A.; Alexander, J.; Becher, G.; Hongslo, J.K.

Mutagenesis 3(4): 303-309

1988

ISSN/ISBN: 0267-8357
PMID: 3062317
DOI: 10.1093/mutage/3.4.303
Accession: 040210584

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Summary
The genotoxic potential of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and their N-acetylated metabolites (AcIQ and AcMeIQ, respectively) has been studied, in order to evaluate whether an initial N-acetylation of IQ or MeIQ is important for the overall in vivo genotoxicity of the compounds. When incubated with uninduced (control) rat hepatocytes, both the acetylated and the unacetylated compounds appeared to be relatively stable, whereas water-soluble metabolites (i.e. not extractable by ethyl acetate at alkaline pH) were rapidly formed with hepatocytes from PCB-induced animals. No DNA damage was induced by IQ or MeIQ in hepatocytes isolated from control rats, as measured by alkaline elution. In hepatocytes from PCB-pretreated rats, IQ, MeIQ, AcIQ and AcMeIQ induced DNA damage at low (10(-6) M) concentrations, with AcIQ being more potent than IQ whereas AcMeIQ was less potent than MeIQ. Similar patterns were observed when unscheduled DNA synthesis was measured in hepatocytes. The compounds induced sister chromatid exchanges in Chinese hamster V79 cells with PCB-induced hepatocytes as activation system; IQ and AcIQ were equal while AcMeIQ had less activity than MeIQ. The compounds were also compared in bacterial mutagenesis test systems (Salmonella typhimurium TA98). With hepatocyte activation, AcIQ was slightly more potent than IQ, whereas AcMeIQ was markedly less mutagenic than MeIQ. With subcellular fractions as activation system (rat liver S9 or microsomes), the N-acetylated compounds were similar to or less mutagenic than their parent compounds. The mutagenic effects of AcIQ and AcMeIQ in bacteria with microsomal activation were markedly reduced by the deacetylase inhibitor paraoxon.

References

Brunborg, G.; Holme, J.A.; Alexander, J.; Becher, G.; Hongslo, J.K. 1988: Genotoxic activity of the n acetylated metabolites of the food mutagens 2 amino 3 methyllimidazo 4 5 f quinoline iq and 2 amino 3 4 dimethylimidazo 4 5 f quinoline meiq Mutagenesis 3(4): 303-310
Pfau, W.; O'Hare, M.J.; Grover, P.L.; Phillips, D.H. 1992: Metabolic activation of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) to DNA binding species in human mammary epithelial cells Carcinogenesis 13(5): 907-909
Edenharder, R.; Von Petersdorff, I. 1991: In vitro effects of flavonoids on the mutagenic action of the cooked food mutagens 2 amino 3 methylimidazo 4 5 f quinoline iq 2 amino 3 4 dimethylimidazo 4 5 f quinoline melq 2 amino 3 8 dimethylimidazo 4 5 f quinoxaline melqx 2 amino 6 methyldipyrido 1 2 a 3 2 d imidazole glu p 1 and 3 amino 1 methyl 5h pyrido 4 3 b indole trp p 2 Zentralblatt fur Hygiene und Umweltmedizin 192(2): 171-172
Alexander, J.; Holme, J.A.; Wallin, H.; Becher, G. 1989: Characterisation of metabolites of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline formed after incubation with isolated rat liver cells Chemico-Biological Interactions 72(1-2): 125-142
Sjodin, P.B.; Nyman, M.E.; Nilsson, L.; Asp N G.L.; Jagerstad, M.I. 1985: Binding of carbon 14 labeled food mutagens 2 amino 3 methylimidazo 4 5 f quinoline 2 amino 3 4 dimethylimidazo 4 5 f quinoline 2 amino 3 8 dimethylimidazo 4 5 f quinoxaline by dietary fiber in vitro Journal of Food Science 50(6): 1680-1684
Størmer, F.C.; Alexander, J.; Becher, G. 1987: Fluorometric detection of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and their N-acetylated metabolites excreted by the rat Carcinogenesis 8(9): 1277-1280
Hall, M.; Shé, M.N.; Wild, D.; Fasshauer, I.; Hewer, A.; Phillips, D.H. 1990: Tissue distribution of DNA adducts in CDF1 mice fed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) Carcinogenesis 11(6): 1005-1011
Holme, J.A.; Alexander, J.; Becher, G.; Trygg, B. 1987: 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 Toxicology in Vitro: An International Journal Published in Association with Bibra 1(4): 175-181
Holme, J.A.; Alexander, J.; Dybing, E. 1987: Mutagenic activation of 2 amino 3 methylimidazo 4 5 f quinoline iq and 2 amino 3 4 dimethylimidazo 4 5 f quinoline meiq by subcellular fractions and cells isolated from small intestine kidney and liver of the rat Cell Biology and Toxicology 3(1): 51-62
Holme, J.A.; Alexander, J.; Dybing, E. 1987: Mutagenic activation of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline (MeIQ) by subcellular fractions and cells isolated from small intestine, kidney and liver of the rat Cell Biology and Toxicology 3(1): 51-61
Holme, J.A.; Brunborg, G.; Alexander, J.; Trygg, B.; Bjørnstad, C. 1988: Modulation of the mutagenic effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in bacteria with rat-liver 9000 x g supernatant or monolayers of rat hepatocytes as an activation system Mutation Research 197(1): 39-49
Holme, J.A.; Brunborg, G.; Alexander, J.; Trygg, B.; Bjornstad, C. 1988: Modulation of the mutagenic effects of 2 amino 3 methylimidazo 4 5 f quinoline iq and 2 amino 3 4 dimethylimidazo 4 5 f quinoline meiq in bacteria with rat liver 9000 x g supernatant or monolayers of rat hepatocytes as an activation system Mutation Research 197(1): 39-50
Waterhouse, A.L.; Rapoport, H. 1985: Synthesis and tritium labeling of the food mutagens iq 2 amino 3 methylimidazo 4 5 f quinoline and methyl iq 2 amino 3 4 dimethylimidazo 4 5 f quinoline methyl iq 2 Journal of Labelled Compounds and Radiopharmaceuticals 22(3): 201-216
2011: Heterocyclic amines (Selected): 2‑amino-3,4-dimethylimidazo[4,5‑f]quinoline, 2‑amino-3,8-dimethylimidazo[4,5‑f]quinoxaline, 2‑amino-3-methylimidazo[4,5‑f]quinoline, 2‑amino-1-methyl-6- phenylimidazo[4,5‑b]pyridine Report on carcinogens: carcinogen profiles 12: 220-224
Edenharder, R.; Kurz, P.; John, K.; Burgard, S.; Seeger, K. 1994: In vitro effect of vegetable and fruit juices on the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 32(5): 443-459
Sadrieh, N.; Synderwine, E.G. 1995: Cytochrome P450 isozymes involved in the metabolic activation of the food mutagens 2-amino-3-methylimidazo quinoline and 2-amino-3, 8-dimethylimidazo quinoxaline in the cynomolgus monkey Proceedings of the American Association for Cancer Research 36: 151
Fay, L.B.; Turesky, R.J. 1992: Electron impact and fast atom bombardment mass spectrometric analysis of the food-borne carcinogens 2-amino-3-methylimidazo [4,5-f] quinoline, 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline and their metabolites Biological Mass Spectrometry 21(9): 463-469
Fay, L.B.; Turesky, R.J. 1992: Electron impact and fast atom bombardment mass spectrometric analysis of the food-borne carcinogens 2-amino-3-methylimidazo[4,5-f] quinoline, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline and their metabolites Biological Mass Spectrometry 21(9): 463-469
Holme, J.A.; Alexander, J.; Becher, G.; Trygg, B. 1987: Metabolism of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) and 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (HeIQ) in suspensions of isolated rat liver cells Toxicology in Vitro 1(4): 175-181
Holme, J.A.; Brunborg, G.; Alexander, J.; Trygg, B.; Søderlund, E.J. 1991: Genotoxic effects of 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) in rats measured by alkaline elution Mutation Research 251(1): 1-6