A comparison of genotoxicity between three common heterocyclic amines and acrylamide.
Heterocyclic amines (HCAs), a group of genotoxic compounds formed during the heating of proteinaceous food items, have been known since the late 1970s. However, the genotoxic effect of these compounds in the low dose region has not yet been thoroughly studied. Here we used a sensitive flow cytometer-based micronucleus assay in mice to determine the frequency of micronucleated erythrocytes (fMPCE) of the three common HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), in the low dose region. We especially looked for any deviation from linearity of the dose-response curves. Male Balb/C mice were intra peritoneally injected with different doses of either PhIP (0-36 mg/kg b.w.), MeIQx (0-90 mg/kg b.w.) or IQ (0-40 mg/kg b.w.). In the case of PhIP, we found a significant dose-response relationship, while MeIQx and IQ did not display an increased fMPCE level. This flow cytometer method allows for determination of the DNA content of micronuclei. All three HCAs tested here yielded a low DNA content of micronuclei, indicating that they do not possess aneugenic effects. A comparison between the HCAs and acrylamide (AA), another heat induced genotoxic compound, revealed that the slope of the dose-response curve is about 10 times steeper for PhIP than AA. In spite of this, AA probably constitutes a higher human risk than HCAs since the intake is about a 100- to 1000-fold higher than the intake of HCAs.
Durling
Louise J K
LJ
Livsmedelsverket, National Food Administration, Toxicology Division, Box 622, SE-75126 Uppsala, Sweden.
Abramsson-Zetterberg
Lilianne
L
D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000633:toxicity*; D007093:Imidazoles / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity; D011810:Quinoxalines / Q000633:toxicity; D013329:Structure-Activity Relationship
D006571:Heterocyclic Compounds; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; D020106:Acrylamide; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine