Document Detail

Different mechanisms involved in apoptosis following exposure to benzo[a]pyrene in F258 and Hepa1c1c7 cells.
MedLine Citation:
PMID:  17289009     Owner:  NLM     Status:  MEDLINE    
The present study compares and elucidates possible mechanisms why B[a]P induces different cell signals and triggers apparently different apoptotic pathways in two rather similar cell lines (hepatic epithelial cells of rodents). The rate and maximal capacity of metabolic activation, as measured by the formation of B[a]P-tetrols and B[a]P-DNA adducts, was much higher in mouse hepatoma Hepa1c1c7 cells than in rat liver epithelial F258 cells due to a higher induced level of cyp1a1. B[a]P increased intracellular pH in both cell lines, but this change modulated the apoptotic process only in F258 cells. In Hepa1c1c7 cells reactive oxygen species (ROS) production appeared to be a consequence of toxicity, unlike F258 cells in which it was an initial event. The increased mitochondrial membrane potential found in F258 cells was not observed in Hepa1c1c7 cells. Surprisingly, F258 cells cultured at low cell density were somewhat more sensitive to low (50nM) B[a]P concentrations than Hepa1c1c7 cells. This could be explained partly by metabolic differences at low B[a]P concentrations. In contrast to the Hepa1c1c7 model, no activation of cell survival signals including p-Akt, p-ERK1/2 and no clear inactivation of pro-apoptotic Bad was observed in the F258 model following exposure to B[a]P. Another important difference between the two cell lines was related to the role of Bax and cytochrome c. In Hepa1c1c7 cells, B[a]P exposure resulted in a "classical" translocation of Bax to the mitochondria and release of cytochrome c, whereas in F258 cells no intracellular translocation of these two proteins was seen. These results suggest that the rate of metabolism of B[a]P and type of reactive metabolites formed influence the resulting balance of pro-apoptotic and anti-apoptotic cell signaling, and hence the mechanisms involved in cell death and the chances of more permanent genetic damage.
Jørn A Holme; Morgane Gorria; Volker M Arlt; Steinar Ovrebø; Anita Solhaug; Xavier Tekpli; Nina E Landvik; Laurence Huc; Olivier Fardel; Dominique Lagadic-Gossmann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-17
Journal Detail:
Title:  Chemico-biological interactions     Volume:  167     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-20     Completed Date:  2007-05-29     Revised Date:  2014-01-08    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  41-55     Citation Subset:  IM    
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MeSH Terms
Aryl Hydrocarbon Hydroxylases / metabolism
Benzo(a)pyrene / toxicity*
Cell Line
Cell Survival / drug effects
Cytochrome P-450 CYP1A1 / metabolism
Epithelial Cells / drug effects*,  metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
Hydrogen-Ion Concentration
Liver / cytology
Membrane Potentials / drug effects
Mitochondria / drug effects,  physiology
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Reactive Oxygen Species / metabolism
bcl-2-Associated X Protein / metabolism
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/bcl-2-Associated X Protein; 3417WMA06D/Benzo(a)pyrene; EC Hydrocarbon Hydroxylases; EC P-450 CYP1A1; EC P-450 CYP1B1; EC Proteins c-akt; EC Signal-Regulated MAP Kinases

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