Identification of 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline: an abundant mutagenic heterocyclic aromatic amine formed in cooked beef.
A previously unknown isomer of the carcinogenic heterocyclic aromatic amine (HAA) 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) was recently discovered in the urine of meat eaters and subsequently detected in cooked ground beef (Holland, R.D., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136). In this current investigation, the identity of the analyte was determined through a comparison of its chromatographic tR by HPLC and through UV and mass spectral comparisons to the synthesized isomers of 8-MeIQx. Angular tricyclic isomers of 8-MeIQx were excluded as potential structures of the newly discovered HAA, on the basis of dissimilar tR and product ion mass spectral data. The linear tricyclic isomers 2-amino-1,6-dimethylimidazo[4,5-g]quinoxaline (6-MeIgQx) and 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline (7-MeIgQx) were postulated as plausible structures. Both compounds were synthesized from 4-fluoro-5-nitro-benzene-1,2-diamine in five steps. The structure of the analyte was proven to be 7-MeIgQx, on the basis of co-injection of the compound with the synthetic isomers, and corroborated by comparisons of the UV and mass spectral data of the analyte and MeIgQx isomers. 7-MeIgQx induced 348 revertants/microg in the S. typhimurium tester strain YG1024, when liver S-9 homogenate of rats pretreated with polychlorinated biphenyls (PCBs) was used for bioactivation. This newly discovered 7-MeIgQx molecule is one of the most abundant HAAs formed in cooked ground beef patties and pan-fried scrapings. The human health risk of 7-MeIgQx requires investigation.
Turesky
Robert J
RJ
Division of Environmental Disease Prevention, Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA. rturesky@wadsworth.org
Goodenough
Angela K
AK
Ni
Weijuan
W
McNaughton
Lynn
L
LeMaster
David M
DM
Holland
Ricky D
RD
Wu
Rebekah W
RW
Felton
James S
JS
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003296:Cooking; D006571:Heterocyclic Compounds / Q000032:analysis* / Q000138:chemical synthesis / Q000633:toxicity*; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008460:Meat / Q000032:analysis*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000032:analysis* / Q000633:toxicity*; D011810:Quinoxalines / Q000032:analysis* / Q000138:chemical synthesis / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
C519626:2-amino-1,7-dimethylimidazo(4,5-g)quinoxaline; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D009153:Mutagens; D011810:Quinoxalines