Identification of candidate biomarkers of the exposure to PCBs in contaminated cattle: A gene expression- and proteomic-based approach

Highlights: • Blood gene expression and protein profiling in PCB exposed heifers were evaluated. • mRNA levels of interleukin 2 and CYP1B1 were correlated with contamination. • MALDI-TOF-MS serum profiling identified 7 differentially represented polypeptides. • A dioxin-responsive network of proteins and genes could serve as biomarker of contamination. Dioxins and polychlorinated biphenyls (PCBs) are widespread and persistent contaminants. Through a combined gene expression/proteomic-based approach, candidate biomarkers of the exposure to such environmental pollutants in cattle subjected to a real eco-contamination event were identified. Animals were removed from the polluted area and fed a standard ration for 6 months. The decontamination was monitored by evaluating dioxin and PCB levels in pericaudal fat two weeks after the removal from the contaminated area (day 0) and then bimonthly for six months (days 59, 125 and 188). Gene expression measurements demonstrated that CYP1B1 expression was significantly higher in blood lymphocytes collected in contaminated animals (day 0), and decreased over time during decontamination. mRNA levels of interleukin 2 showed an opposite quantitative trend. MALDI-TOF-MS polypeptide profiling of serum samples ascertained a progressive decrease (from day 0 to 188) of serum levels of fibrinogen β-chain and serpin A3-7-like fragments, apolipoprotein (APO) C-II and serum amyloid A-4 protein, along with an augmented representation of transthyretin isoforms, as well as APOC-III and APOA-II proteins during decontamination. When differentially represented species were combined with serum antioxidant, acute phase and proinflammatory protein levels already ascertained in the same animals (Cigliano et al., 2016), bioinformatics unveiled an interaction network linking together almost all components. This suggests the occurrence of a complex PCB-responsive mechanism associated with animal contamination/decontamination, including a cohort of protein/polypeptide species involved in blood redox homeostasis, inflammation and lipid transport. All together, these results suggest the use in combination of such biomarkers for identifying PCB-contaminated animals, and for monitoring the restoring of their healthy condition following a decontamination process.