Evaluation of toxicological monitoring markers using proteomic analysis

Abstract

In our study, we chose three different concentrations of FA (0, 5, and 10 ppm), and cytotoxic (lipid peroxidation and protein oxidation) and genotoxic assays (DNA damage) were carried out on plasma, blood, and liver cells of rats subjected to FA-inhalation treatment. The profiles of plasma protein changes determined using 2-DE analysis were also evaluated to identify potential toxicological monitoring markers in FA-exposed rats. Concern was raised that our genotoxic analyses did not follow previously published research data and that the results of our rat plasma proteomic studies were difficult to interpret because we did not directly determine the plasma concentration of FA. However, we had already determined the concentration of FA using HPLC in an exposure chamber to monitor FA inhalation concentrations. We suggest that our experimental design was suitable to determine the FA effects on rat using an inhalation chamber system. For the similarity of genotoxic effects in lymphocytes and liver cells, we chose to present our data on the general cytological toxic effects on lipid peroxidation and protein oxidation which revealed a similarity between plasma and liver cells of FA-exposed rats. We have shown strong correlations between genotoxicity and lipid peroxidation, and lipid peroxidation is known to mediate DNA damage in many in vitro, and in vivo studies. We are well aware of the 'implausibility' of leukemia induction by FA, but for precisely this reason, we feel the need for further study to prove the systemic genotoxic effects of FA.