Metabonomics biomarkers for subacute toxicity screening for benzene exposure in mice.
Benzene is known to produce hematotoxicity in occupational exposure workers. This study examined the utility of metabonomic biomarkers to ascertain subacute toxicity produced by benzene in male C3H/He mice. A 30-d intermittent collection of urine was obtained from mice in this experiment. The relative organ weights, blood parameters, and bone marrow smears were examined to identify specific changes of benzene-induced toxicity. In addition, an integrated analytical approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to map metabolic responses in urine. Five endogenous metabolites, hypoxanthine, spermidine, 4-aminohippuric acid, indolelactic acid, and glutamylphenylalanine, were identified as potential biomarkers of benzene-induced toxicity, indicating that pathways of purine, spermidine, fatty acid, tryptophan, and peptides metabolism might be disturbed in benzene-exposed mice. Our findings showed that the use of urine metabonomics was a more sensitive tool to detect benzene-induced toxicity compared to body weight or blood parameter changes.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China.
Rongli
R
Sun
Juan
J
Zhang
Mengzhen
M
Xiong
Yue
Y
Chen
Lihong
L
Yin
Yuepu
Y
Pu
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D002274:Carcinogens, Environmental / Q000633:toxicity*; D004151:Dipeptides / Q000652:urine; D004305:Dose-Response Relationship, Drug; D019271:Hypoxanthine / Q000652:urine; D007211:Indoles / Q000652:urine; D007279:Injections, Subcutaneous; D007700:Kinetics; D008297:Male; D008403:Mass Screening / Q000379:methods; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D025341:Principal Component Analysis; D011897:Random Allocation; D012997:Solvents / Q000633:toxicity*; D013095:Spermidine / Q000652:urine; D010130:p-Aminohippuric Acid / Q000652:urine
D015415:Biomarkers; D002274:Carcinogens, Environmental; D004151:Dipeptides; D007211:Indoles; D012997:Solvents; D019271:Hypoxanthine; C024139:indole-3-lactic acid; C020621:gamma-glutamylphenylalanine; D001554:Benzene; D013095:Spermidine; D010130:p-Aminohippuric Acid