Identification of Three New Mutagenic Heterocyclic Amines and Human Exposure to Known Heterocyclic Amines

We identified three new mutagenic heterocyclic amines (HCAs), 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4, 5- b ]pyridine (4'-OH-PhIP) in broiled beef, and 2-amino-4-hydroxymethyl-3, 8-dimethylimidazo[4, 5- f ]quinoxaline (4-CH 2 OH-8-McIQx) and 2-amino-1, 7,9-trimethylimidazo[4, 5- g ]quinoxaline (7, 9-DiMelgQx) in beef extract. The level of 4'-OH-PhIP was 21 ng/g in broiled beef, and the levels of 4-CH 2 OH-8-MeIQx and 7, 9-DiMeI g Qx were 6.0 and 53 ng/g, respectively, in beef extract. The mutagenicity of 4'-OH-PhIP to TA98 with S9 mix was 180 revertants/100 μg. 4-CH 2 OH-8-MeIQx and 7, 9-DiMeI g Qx induced 326, 000 and 13, 800 revertants of YG1024, and 99, 000 and 670 revertants of TA98 per mg, respectively, in the presence of S9 mix. Furthermore, 4'-OH-PhIP was demonstrated to be formed by heating a mixture of creatine, tyrosine and glucose. Similarly, creatine, threonine and sugars were found to be involved in the formations of 4-CH 2 OH-8-MeIQx and 7, 9-DiMeI g Qx. Thus, the Maillard reaction is associated with the formation of the newly identified mutagenic HCAs, like other known 2-amino-3-methylimidazo[4, 5- f ]quinoline (IQ)-type HCAs.