Effects of citrus flavonoids on the mutagenicity of heterocyclic amines and on cytochrome p450 1A2 activity

Heterocyclic amines (HCA's) are promutagens produced by high temperature co oking of meat products and are activated by cytochrome P450 (CYP) 1A2. Usin g Aroclor 1254 induced rat liver S9 we tested foul citrus flavonoids diosmi n, naringenin, naringin and rutin for their effects on the mutagenicity of HCA's MeIQx Glu-P-1*, IQ and PhIP in Salmonella typhimurium TA98. The effec ts of the citrus flavonoids or? CYPlA2 activity was determined by measuring demethylation of methoxyresorufin (MROD). MeIQx induced mutagenesis in S. typhimurium was significantly inhibited by all forts flavonoid's in a conce ntration dependent manner at 0.25 0.5 and 1.0 mu mole. Glu-P-1 induced muta genesis was inhibited by rutin and naringenin. IQ induced mutagenesis was s ignificantly inhibited by each flavonoid except diosmin at all three doses. With the exception of diosmin and naringin at 0.25 mu mole all four flavon oids at all three closes significantly inhibited PhlP induced mutagenesis. The inhibition of MROD activity by the citrus flavonoids correlated best wi th the inhibition of MeIQx induced mutagenesis brit also correlated with th e inhibition of IQ induced mutagenesis except for diosmin and with the inhi bition of PhlP induced mutagenesis except for the 0.25 mu mole dose of dios min and naringin. Our. data suggest a chemopreventive potential for diosmin , naringin, naringenin and rutin towards CYPlA2 mediated mutagenesis of HCA 's.