[Screening of biomarkers in exhaled breath of mice exposed to benzene].

Objective: To screen the biomarkers in the exhaled breath of mice exposed to benzene by using exhaled breath online analysis system. Methods: Thirty 8-week-old male C57BL/6 mice were randomly divided into six groups (0, 3, 32, 324, 648, and 1 296 mg/m ³ ) and treated with benzene vapour for 28 days. At the end of the exposure, the peripheral blood cell counts and blood glutathione (GSH) were detected. The content of malondialdehyde (MDA) in HL60 cells treated by mice plasma was examined. Exhaled breath data from mice were collected by Secondary electrospray ionization source high resolution mass spectrometry (SESI-HRMS). Targeted analysis underlying benzene metabolites and oxidative stress metabolites was performed to screen the biomarkers in exhaled breath. Results: After benzene exposure, the number of peripheral blood cells was decreased in different degrees, particularly in the white blood cells (WBC) number. The WBC in 32 and 324 mg/m ³ groups was declined by 27.76% and 52.87%, respectively compared to that in control group ( P <0.05). Meanwhile, compared with the control group, the GSH content of peripheral blood cells from 324 mg/m ³ group decreased by 13.16% ( P <0.05). In addition, MDA content was increased by 18.11% in HL60 cells treated with plasma from 324 mg/m ³ group mice ( P <0.05). The phenol, hydroquinone/catechol, benzenetriol and trans , trans -Muconic acid ( t,t -MA) in the exhaled gas of mice could be used as biomarkers for benzene exposure ( R ² >0.8, P <0.001). The peak intensity of five small molecular metabolites related to oxidative stress (ω-carboxylic fatty acid C ₅ H ₁₀ O ₃ , ω-carboxylic fatty acid C ₆ H ₁₂ O ₃ , glutamate, cysteine and MDA) increased with the increase of benzene concentration ( P <0.05), which was negatively correlated with WBC decline ( P <0.001), suggesting that these molecules mignt be used as biomarkers of benzene-induced toxicity. Conclusions: Phenol, hydroquinone/catechol, benzenetriol and trans , trans -Muconic acid ( t,t -MA) in exhaled breath of mice could be used as biomarkers for benzene exposure; ω-carboxylic fatty acid C ₅ H ₁₀ O ₃ , ω-carboxylic fatty acid C ₆ H ₁₂ O ₃ , glutamate, cysteine and MDA might be used as markers of benzene-induced toxicity.