Food-derived heterocyclic amines potentiate the mutagenicity of a drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX).
We investigated the enhancing effect of heterocyclic amines on base-substitution mutations with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (MeIQ). We compared the mutagenicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the presence and absence of the heterocyclic amines in E. coli WP2 (trpE) and in excision repair-deficient strains WP2s (uvrA, trpE) and ZA500 (uvrA, rfa, trpE). Since the assay was performed without microsomal metabolic activation, Trp-P-1 and MeIQ alone were not mutagenic. In WP2, trp+ reversions induced by MX were greatly potentiated by Trp-P-1 and slightly potentiated by MeIQ. Mutation enhancement was not observed in strains WP2s and ZA500, suggesting that a functional DNA excision repair system is necessary for the combined action of MX and heterocyclic amines. Our finding implies that the combined effect of mutagens as well as the effect of individual mutagens, should be considered in risk evaluation.
Watanabe-Akanuma
M
M
Toxicology Division, Institute of Environmental Toxicology, Tokyo, Japan.
Shimoi
K
K
Kinae
N
N
Ohta
T
T
D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000235:genetics; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics; D002243:Carbolines / Q000494:pharmacology*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins; D005663:Furans / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011804:Quinolines / Q000494:pharmacology*
D001426:Bacterial Proteins; D002243:Carbolines; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005663:Furans; D009153:Mutagens; D011804:Quinolines; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole