Metabolite Profiling to Monitor Organochlorine Pesticide Exposure in HepG2 Cell Culture

Gas chromatography coupled with time of flight mass spectrometry (GC/MS-TOF) was used to profile endogenous metabolites in HepG2 cell cultures to assess the metabolic changes induced by exposure to different organochlorine pesticides, their mixtures and controls (endosulfan, lindane, DDT and aldrin). Cells were cultured in DMEM with Glutamax at 37 A degrees C with 5 % CO2 for 72 h and then exposed to each pesticide, pesticide mixture or DMSO (as a control) for 24 h, and finally, endogenous metabolites were extracted and analyzed using GC/MS-TOF. The experiment was repeated six times under the same cell passage and culture conditions. PCA, PLS-DA and ROC were performed to analyze the GC/MS-TOF data and identify potential biomarkers. Thirty-five explanatory metabolites were found in both PCA and PLS-DA models, where Q (2) was 0.86 and R (2) was 0.98. Univariate and multivariate ROC showed potential biomarkers for each treatment, suggesting a general toxic mechanism for organochlorine pesticides that is specific for each type of compound. These results confirmed the effect of OCPs in sugar and amino acid metabolism that are linked with the function of cytochrome P450 in reductive dechlorination and oxidative stress.