Metabonomics Biomarkers for Subacute Toxicity Screening for Benzene Exposure in Mice

Abstract

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.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No: 30901168) and the Doctoral Fund of Ministry of Education of China (Grant No: 20100092120054), the National Natural Science Foundation of Jiangsu province (Grant No: BK2011605).

Notes

Rongli Sun and Juan Zhang contributed equally to this work.