Different mechanisms involved in apoptosis following exposure to benzo[a]pyrene in F258 and Hepa1c1c7 cells.

2.50
Hdl Handle:
http://hdl.handle.net/10146/25214
Title:
Different mechanisms involved in apoptosis following exposure to benzo[a]pyrene in F258 and Hepa1c1c7 cells.
Authors:
Holme, Jorn A.; Gorria, Morgane; Arlt, Volker M.; Ovrebo, Steinar; Solhaug, Anita; Tekpli, Xavier; Landvik, Nina E.; Huc, Laurence; Fardel, Olivier; Lagadic-Gossmann, Dominique
Abstract:
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.
Citation:
Chem. Biol. Interact. 2007, 167(1):41-55
Journal:
Chemico-biological Interactions
Issue Date:
5-Apr-2007
URI:
http://hdl.handle.net/10146/25214
DOI:
10.1016/j.cbi.2007.01.008
PubMed ID:
17289009
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T56-4MV757D-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=30d4f8f1085dde89d9170344e9f7fba5
Type:
Article
Language:
en
ISSN:
0009-2797
Sponsors:
The study has been supported by an Aurora grant (Egide) and Cancer Research, UK and the financial support is greatly appreciated. Volker M. Arlt is a member of the Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) EU Network of Excellence. We thank Ingrid V. Botnen and Leni Ekeren for skilled technical assistance. We wish to thank the microscopy platform and Dr. Dutertre (UMR 6061, CNRS, Rennes) for helpful advice on immunolocalization captures and analyzes.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorHolme, Jorn A.-
dc.contributor.authorGorria, Morgane-
dc.contributor.authorArlt, Volker M.-
dc.contributor.authorOvrebo, Steinar-
dc.contributor.authorSolhaug, Anita-
dc.contributor.authorTekpli, Xavier-
dc.contributor.authorLandvik, Nina E.-
dc.contributor.authorHuc, Laurence-
dc.contributor.authorFardel, Olivier-
dc.contributor.authorLagadic-Gossmann, Dominique-
dc.date.accessioned2008-05-09T10:55:00Z-
dc.date.available2008-05-09T10:55:00Z-
dc.date.issued2007-04-05-
dc.identifier.citationChem. Biol. Interact. 2007, 167(1):41-55en
dc.identifier.issn0009-2797-
dc.identifier.pmid17289009-
dc.identifier.doi10.1016/j.cbi.2007.01.008-
dc.identifier.urihttp://hdl.handle.net/10146/25214-
dc.description.abstractThe 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.en
dc.description.sponsorshipThe study has been supported by an Aurora grant (Egide) and Cancer Research, UK and the financial support is greatly appreciated. Volker M. Arlt is a member of the Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) EU Network of Excellence. We thank Ingrid V. Botnen and Leni Ekeren for skilled technical assistance. We wish to thank the microscopy platform and Dr. Dutertre (UMR 6061, CNRS, Rennes) for helpful advice on immunolocalization captures and analyzes.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T56-4MV757D-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=30d4f8f1085dde89d9170344e9f7fba5en
dc.subjectBenzo[a]pyreneen
dc.subjectCell signalingen
dc.subjectDNA adductsen
dc.subjectMetabolismen
dc.subjectApoptosisen
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshAryl Hydrocarbon Hydroxylases-
dc.subject.meshBenzo(a)pyrene-
dc.subject.meshCell Line-
dc.subject.meshCell Survival-
dc.subject.meshCytochrome P-450 CYP1A1-
dc.subject.meshEpithelial Cells-
dc.subject.meshExtracellular Signal-Regulated MAP Kinases-
dc.subject.meshHydrogen-Ion Concentration-
dc.subject.meshLiver-
dc.subject.meshMembrane Potentials-
dc.subject.meshMice-
dc.subject.meshMitochondria-
dc.subject.meshProto-Oncogene Proteins c-akt-
dc.subject.meshProto-Oncogene Proteins c-bcl-2-
dc.subject.meshRats-
dc.subject.meshReactive Oxygen Species-
dc.subject.meshbcl-2-Associated X Protein-
dc.titleDifferent mechanisms involved in apoptosis following exposure to benzo[a]pyrene in F258 and Hepa1c1c7 cells.en
dc.typeArticleen
dc.identifier.journalChemico-biological Interactionsen

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