Abstract
Metabolomics has been used to explore the molecular mechanism and screen biomarkers. However, the critical metabolic signatures associated with benzene-induced hematotoxicity remain elusive. Here, we performed a plasma metabolomics study in 86 benzene-exposed workers and 76 healthy controls, followed by a validation analysis in mice, to investigate the dynamical change of the metabolic profile. We found that 8 fatty acids were significantly altered in both benzene-exposed worker and benzene-exposed animal models. These metabolites were significantly associated with S-phenylmercapturic acid and WBC, and they mediated the benzene-induced WBC decline. Furthermore, in vivo results confirm that fatty acid levels were dynamically altered, characterized by a decrease at 15 days and then sharp increases at 30 and 45 days. Following these identified fatty acids, the potential metabolic pathways were investigated. Fatty acids, as precursors for fatty acid oxidation, may disturb the balance of fatty acid biosynthesis and degradation. Our results reveal that fatty acid metabolism was strongly reprogrammed after benzene exposure. This abnormal change of fatty acids might be the key metabolic signature associated with benzene-induced hematotoxicity.
Highlights
Benzene continues to be a nonnegligible contributor to leukemia in occupationally and environmentally exposed populations
We found that differences in urinary S-phenylmercapturic acid (SPMA) and trans-muconic acid (tt-MA) levels were significantly identified in both groups, with SPMA being significantly elevated in benzene-exposed workers (P < 0.05), suggesting that SPMA might be a sensitive marker of low-level benzene exposure
We only found that the hemoglobin (HGB) level was higher than that in control group (P < 0.05), and alanine transaminase (ALT), a sensitive marker of hepatocellular damage, was remarkably increased in benzene-exposed female workers with the mean value of 22.50 U/L
Summary
Benzene continues to be a nonnegligible contributor to leukemia in occupationally and environmentally exposed populations. Recent epidemiological studies have shown that global acute myelocytic leukemia (AML) morbidity and mortality have been increasing over the past 28 years and that occupational exposure to benzene is considered a major risk factor [1]. Previous studies have shown that workers exposed to 1 ppm benzene exhibited no substantial WBC harm, but their BM hematopoietic capability was severely reduced in terms of renewal and differentiation [3]. This result suggested the limitations of a single WBC indicator for diagnosing hematologic adverse events caused by low-level benzene exposure. Discovering potential biomarkers to identify high-risk individuals earlier is crucial for developing effective strategies to prevent chronic benzene poisoning and leukemia
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