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Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Abstract : Benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, which has led the International Agency for Research on Cancer to recognize it as a human carcinogen. Besides the well-known apoptotic signals triggered by B[a]P, survival signals have also been suggested to occur, both signals likely involved in cancer promotion. Our previous work showed that B[a]P induced an hyperpolarization of mitochondrial membrane potential (ΔΨm) in rat hepatic epithelial F258 cells. Elevated ΔΨm plays a role in tumor development and progression, and nitric oxide (NO) has been suggested to be responsible for increases in ΔΨm. The present study therefore aimed at evaluating the impact of B[a]P on NO level in F258 cells, and at testing the putative role for NO as a survival signal, notably in link with ΔΨm. Our data demonstrated that B[a]P exposure resulted in an NO production which was dependent upon the activation of the inducible NO synthase. This enzyme activation involved AhR and possibly p53 activation. Preventing NO production not only increased B[a]P-induced cell death but also blocked mitochondrial hyperpolarization. This therefore points to a role for NO as a survival signal upon B[a]P exposure, possibly targeting ΔΨm
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Submitted on : Thursday, November 19, 2015 - 12:18:14 PM
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Kevin Hardonnière, Laurence Huc, Normand Podechard, Morgane Fernier, Xavier Tekpli, et al.. Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential. Toxicology in Vitro, Elsevier, 2015, 29 (7), pp.1597-1608. ⟨10.1016/j.tiv.2015.06.010⟩. ⟨hal-01163757⟩

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