Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1021/pr500957t
Title (Primary) Pathway and time-resolved benzo[a]pyrene toxicity on Hepa1c1c7 cells at toxic and subtoxic exposure
Author Kalkhof, S.; Dautel, F.; Loguercio, S.; Baumann, S.; Trump, S.; Jungnickel, H.; Otto, W.; Rudzok, S.; Potratz, S.; Luch, A.; Lehmann, I.; Beyer, A.; von Bergen, M.
Source Titel Journal of Proteome Research
Year 2015
Volume 14
Issue 1
Page From 164
Page To 182
Language englisch
Keywords Benzo[a]pyrene (B[a]P); aryl hydrocarbon receptor (Ahr); oxidative stress; protein expression analysis; SILAC; proteomics; metabolomics; Hepa1c1c7 cells; B[a]P metabolites
UFZ wide themes RU3;
Abstract Benzo[a]pyrene (B[a]P) is an environmental contaminant mainly studied for its toxic/carcinogenic effects. For a comprehensive and pathway orientated mechanistic understanding of the effects directly triggered by a toxic (5 μM) or a subtoxic (50 nM) concentration of B[a]P or indirectly by its metabolites, we conducted time series experiments for up to 24 h to study the effects in murine hepatocytes. These cells rapidly take up and actively metabolize B[a]P, which was followed by quantitative analysis of the concentration of intracellular B[a]P and seven representative degradation products. Exposure with 5 μM B[a]P led to a maximal intracellular concentration of 1604 pmol/5 × 104 cells, leveling at 55 pmol/5 × 104 cells by the end of the time course. Changes in the global proteome (>1000 protein profiles) and metabolome (163 metabolites) were assessed in combination with B[a]P degradation. Abundance profiles of 236 (both concentrations), 190 (only 5 μM), and 150 (only 50 nM) proteins were found to be regulated in response to B[a]P in a time-dependent manner. At the endogenous metabolite level amino acids, acylcarnitines and glycerophospholipids were particularly affected by B[a]P. The comprehensive chemical, proteome and metabolomic data enabled the identification of effects on the pathway level in a time-resolved manner. So in addition to known alterations, also protein synthesis, lipid metabolism, and membrane dysfunction were identified as B[a]P specific effects.

Persistent UFZ Identifier
Kalkhof, S., Dautel, F., Loguercio, S., Baumann, S., Trump, S., Jungnickel, H., Otto, W., Rudzok, S., Potratz, S., Luch, A., Lehmann, I., Beyer, A., von Bergen, M. (2015):
Pathway and time-resolved benzo[a]pyrene toxicity on Hepa1c1c7 cells at toxic and subtoxic exposure
J. Proteome Res. 14 (1), 164 - 182 10.1021/pr500957t