Formation of a Mutagenic Heterocyclic Aromatic Amine from Creatinine in Urine of Meat Eaters and Vegetarians

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• 作者：Ricky D. Holland ; Theresa Gehring ; Jason Taylor ; Brian G. Lake ; Nigel J. Gooderham ; and Robert J. Turesky
• 刊名：Chemical Research in Toxicology
• 出版年：2005
• 出版时间：March 2005
• 年：2005
• 卷：18
• 期：3
• 页码：579 - 590
• 全文大小：472K
• 年卷期：v.18,no.3(March 2005)
• ISSN：1520-5010

文摘

Liquid chromatography electrospray ionization mass spectrometry (MS) with a triplequadrupole MS was used to identify known and novel heterocyclic aromatic amines (HAAs) inhuman urine. The identities of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were confirmed by their product ionspectra. The constant neutral loss scan mode was employed to probe for other analytes inurine that display the transition [M + H]⁺ ages/entities/rarr.gif"> [M + H - CH₃^{ages/entities/bull.gif">}]^{+ages/entities/bull.gif">}, which is common to HAAscontaining an N-methylimidazo moiety, and led to the detection of a previously unreportedisomer of 8-MeIQx [Holland, R., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136]. We nowreport the identification of another novel HAA, 2-amino-1-methylimidazo[4,5-b]quinoline(IQ[4,5-b]), an isomer of the powerful animal carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The amounts of IQ[4,5-b] measured in the urine of human volunteers whoconsumed grilled beef ranged from 15 to 135% of the ingested dose, while the amounts of8-MeIQx and PhIP excreted in urine were on average <2% of the ingested dose. Base treatmentof urine at 70 ages/entities/deg.gif">C increased the concentrations of 8-MeIQx and PhIP by as much as 6-fold,indicating the presence of phase II conjugates; however, the amount of IQ[4,5-b] increased bymore than 100-fold. IQ[4,5-b] was also detected in the urine of vegetarians following basehydrolysis. The formation of IQ[4,5-b], but not IQ, 8-MeIQx, or PhIP, also occurred in urineincubated at 37 ages/entities/deg.gif">C. Creatinine and 2-aminobenzaldehyde are likely precursors of IQ[4,5-b].The detection of IQ[4,5-b] in the urine of both meat eaters and vegetarians suggests that thisHAA may be present in nonmeat staples or that IQ[4,5-b] formation may occur endogenouslywithin the urinary bladder or other biological fluids.