Pathway and Time-Resolved
Benzo[a]pyrene Toxicity on Hepa1c1c7 Cells at Toxic
and Subtoxic Exposure
Posted on 2015-01-02 - 00:00
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.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Kalkhof, Stefan; Dautel, Franziska; Loguercio, Salvatore; Baumann, Sven; Trump, Saskia; Jungnickel, Harald; et al. (2016). Pathway and Time-Resolved
Benzo[a]pyrene Toxicity on Hepa1c1c7 Cells at Toxic
and Subtoxic Exposure. ACS Publications. Collection. https://doi.org/10.1021/pr500957t
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (13)
SK
Stefan Kalkhof
FD
Franziska Dautel
SL
Salvatore Loguercio
SB
Sven Baumann
ST
Saskia Trump
HJ
Harald Jungnickel
WO
Wolfgang Otto
SR
Susanne Rudzok
SP
Sarah Potratz
AL
Andreas Luch
IL
Irina Lehmann
AB
Andreas Beyer
MB
Martin von Bergen