Antimutagenicity of Maillard reaction products from amino acid/sugar model systems against 2-amino-3-methylimidazo-[4, 5-f]quinoline: The role of pyrazines

The antimutagenicity of dichloromethane extracts from eight amino acid/sugar model systems was determined using Salmonella typhimurium TA98 against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the presence of Aroclor 1254-induced rat hepatic S9. The Maillard reaction products in the dichloromethane extracts were then quantified and qualified by capillary gas chromatography and gas chromatography-mass spectrometry, respectively. Pyrazines and furans were found to be the major Maillard reaction products yielded in the extracts. Moreover, the antimutagenicity of dichloromethane extracts correlated positively with the total amounts of pyrazines and furans. To elucidate the mechanism of antimutagenicity of dichloromethane extracts, the inhibitory effect of pyrazines on ethoxycoumarin deethylase activity in Aroclor 1254-induced hepatic microsomes was examined. We also studied the effects of pyrazines on IQ metabolism by Aroclor 1254-induced microsomes using high-performance liquid chromatography. The antimutagenicity of pyrazines correlated positively with both the inhibition of cytochrome P-450 IA2-linked ethoxycoumarin deethylase in hepatic microsomes and the inhibition of N-hydroxy-IQ formation from IQ metabolism by hepatic microsomes. Thus we concluded that pyrazines in dichloromethane extracts from eight amino acid/sugar model systems play an important role in the antimutagenicity of IQ. Moreover, we concluded that the modifying effect of pyrazines on the mutagenicity of IQ is mediated through interaction with microsomal activating enzymes to inhibit the major active metabolite in N-hydroxy-IQ formation.