Metabolomic Study of Urine from Workers Exposed to Low Concentrations of Benzene by UHPLC-ESI-QToF-MS Reveals Potential Biomarkers Associated with Oxidative Stress and Genotoxicity

Abstract

Benzene is a human carcinogen whose exposure to concentrations below 1 ppm (3.19 mg.m−3) is associated with myelotoxic effects. The determination of biomarkers such as trans-trans muconic acid (AttM) and S-phenylmercapturic acid (SPMA) show exposure without reflecting the toxic effects of benzene. For this reason, in this study, the urinary metabolome of individuals exposed to low concentrations of benzene was investigated, with the aim of understanding the biological response to exposure to this xenobiotic and identifying metabolites correlated with the toxic effects induced by it. Ultra-efficient liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer (UHPLC-ESI-Q-ToF-MS) was used to identify metabolites in the urine of environmentally (n = 28) and occupationally exposed (n = 32) to benzene (mean of 22.1 μg.m−3 and 31.8 μg.m−3, respectively). Non-targeted metabolomics analysis by PLS-DA revealed nine urinary metabolites discriminating between groups and statistically correlated with oxidative damage (MDA, thiol) and genetic material (chromosomal aberrations) induced by the hydrocarbon. The analysis of metabolic pathways revealed important alterations in lipid metabolism. These results point to the involvement of alterations in lipid metabolism in the mechanisms of cytotoxic and genotoxic action of benzene. Furthermore, this study proves the potential of metabolomics to provide relevant information to understand the biological response to exposure to xenobiotics and identify early effect biomarkers.

An Exploratory Study of the Metabolite Profiling from Pesticides Exposed Workers

“…They have essential homeostatic functions in renal physiology, are potent vasodilators and platelet aggregation inhibitors but are also implicated in many pathological conditions, such as inflammation, cardiovascular disease and the initiation of carcinogenesis, representing the link between inflammation and cancer. Under normal conditions, levels of prostanoids in cells are low, but during a disturbance, their concentration can be altered [ 13 , 35 ].…”

“…This technique provides an integrated view of biochemistry in complex systems and, in the area of occupational and environmental toxicology, is especially useful in the identification of new biomarkers of chemical contaminants, in addition to exhibiting great potential for clarifying the mechanisms of toxicity of these agents as well as investigating metabolism and other possible biological interactions. There are some challenges involved with metabolomics, such as the analytical process, which is critical, in addition to difficulties involved with reproducing the data necessary for the replication of studies or even their continuity after the discovery of biomarkers [ 11 , 12 , 13 , 14 ].…”

Network Analysis of Biomarkers Associated with Occupational Exposure to Benzene and Malathion

“…The fact that one can observe similar disease phenotypes despite different genetic causes suggests that these different causes are not unrelated but rather jointly contribute to dysregulating the same component of the cellular system [1]. However, it is worth noting that exposure to low concentrations of environmental and occupational carcinogens does not eliminate the risk, considering that there is no safe exposure limit to carcinogenic substances such as benzene and malathion [77][78][79].…”