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, 1121−113...

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Published in:Chemical research in toxicology 2007-03, Vol.20 (3), p.520-530
Main Authors: Turesky, Robert J, Goodenough, Angela K, Ni, Weijuan, McNaughton, Lynn, LeMaster, David M, Holland, Ricky D, Wu, Rebekah W, Felton, James S
Format: Article
Language:English
Subjects:
Animals
Cattle
Chromatography, High Pressure Liquid
Cooking
Heterocyclic Compounds - analysis
Heterocyclic Compounds - chemical synthesis
Heterocyclic Compounds - toxicity
Indicators and Reagents
Mass Spectrometry
Meat - analysis
Mutagenicity Tests
Mutagens - analysis
Mutagens - toxicity
Quinoxalines - analysis
Quinoxalines - chemical synthesis
Quinoxalines - toxicity
Salmonella typhimurium
Salmonella typhimurium - drug effects
Salmonella typhimurium - genetics
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
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Summary: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 t R 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 t R 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/μg 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.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx600317r