Environmental carcinogenesis and pH homeostasis: Not only a matter of dysregulated metabolism

Hardonnière, Kévin; Huc, Laurence; Sergent, Odile; Holme, Jørn A.; Lagadic‐Gossmann, Dominique

doi:10.1016/j.semcancer.2017.01.001

Cited by 34 publications

(27 citation statements)

References 217 publications

(334 reference statements)

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“…As no difference was detected regarding CYP1B1 expression (and so for the expression of both CYP3A1 and epoxide hydrolases EPHX1 and EPHX2) between steatosis and non-steatosis conditions ( Supplementary Fig. S3), and due to the fact that WIF-B9 cells constitutively express CYP1A1 [46] which plays an important role in B[a]P metabolism [44], we decided to focus on the expression of this CYP. Data in Fig.…”

Section: Role For Effector Caspases and Activationmentioning

confidence: 99%

“…As AhR (aryl hydrocarbon receptor) has been previously shown to play a role in the regulation of liver ADH expression [53] and based upon the fact that αNF, a known antagonist of AhR in addition to be a CYP1 inhibitor, prevented the cell death induced by co-exposure in steatotic cells ( Fig. 2A), we decided to test a possible role for this B[a]P-activated receptor [44]. Fig.…”

Section: Role For Effector Caspases and Activationmentioning

confidence: 99%

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Mechanisms involved in the death of steatotic WIF-B9 hepatocytes co-exposed to benzo[a]pyrene and ethanol: a possible key role for xenobiotic metabolism and nitric oxide

Tête

Gallais

Imran

et al. 2018

Free Radical Biology and Medicine

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We previously demonstrated that co-exposing pre-steatotic hepatocytes to benzo[a]pyrene (B[a]P), a carcinogenic environmental pollutant, and ethanol, favored cell death. Here, the intracellular mechanisms underlying this toxicity were studied. Steatotic WIF-B9 hepatocytes, obtained by a 48hsupplementation with fatty acids, were then exposed to B[a]P/ethanol (10 nM/5 mM, respectively) for 5 days. Nitric oxide (NO) was demonstrated to be a pivotal player in the cell death caused by the coexposure in steatotic hepatocytes. Indeed, by scavenging NO, CPTIO treatment of co-exposed steatotic cells prevented not only the increase in DNA damage and cell death, but also the decrease in the activity of CYP1, major cytochrome P450s of B[a]P metabolism. This would then lead to an elevation of B[a]P levels, thus possibly suggesting a long-lasting stimulation of the transcription factor AhR. Besides, as NO can react with superoxide anion to produce peroxynitrite, a highly oxidative compound, the use of FeTPPS to inhibit its formation indicated its participation in DNA damage and 1 equal supervision 2 cell death, further highlighting the important role of NO. Finally, a possible key role for AhR was pointed out by using its antagonist, CH-223191. Indeed it prevented the elevation of ADH activity, known to participate to the ethanol production of ROS, notably superoxide anion. The transcription factor, NFB, known to be activated by ROS, was shown to be involved in the increase in iNOS expression. Altogether, these data strongly suggested cooperative mechanistic interactions between B[a]P via AhR and ethanol via ROS production, to favor cell death in the context of prior steatosis.

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Section: Role For Effector Caspases and Activationmentioning

confidence: 99%

Section: Role For Effector Caspases and Activationmentioning

confidence: 99%

Mechanisms involved in the death of steatotic WIF-B9 hepatocytes co-exposed to benzo[a]pyrene and ethanol: a possible key role for xenobiotic metabolism and nitric oxide

Tête

Gallais

Imran

et al. 2018

Free Radical Biology and Medicine

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“…Mitochondria play an important role in oxidative stress upon AhR activation by environmental contaminants, with a AhR-dependent ROS production, a mitochondrial membrane hyperpolarization, a mitochondrial matrix acidification and a decrease in mitochondrial electron transport chain activity in liver cells [29][30][31]. AhR was demonstrated to interact with a subunit of the ATPase synthase M A N U S C R I P T…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Nrf2 and AhR in metabolic reprogramming after contaminant exposure

Bortoli

Boutet-Robinet

Lagadic‐Gossmann

et al. 2018

Current Opinion in Toxicology

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International audienceBeside their crucial role in xenobiotic biotransformation, AhR and Nrf2 are involved in the regulation of energetic metabolism. Nrf2, as a cytoprotective transcription factor, supply energy for detoxification and antioxidant response. AhR is ligand-activated transcriptional factor implicated in several physiological function. Following pollutant exposure, it acts as a chemosensor to eliminate harmful chemicals. Altogether, AhR and Nrf2 cooperate to contribute to protective responses upon contaminant exposure, including metabolic remodelling. This fine-tuned energetic coupling with detoxification can lead to prominent dysfunction under a chronic exposure to pollutants, and promote a long-term reprogramming that affects multiple cellular activities. In the article, we review the involvement of Nrf2 and AhR in the metabolic adaptations that occur during the short-term cell defence upon toxicant exposure, and in the metabolic reprogramming caused by their sustained activation. We also provide several clues to highlight the potential role of the Nrf2/AhR-induced metabolic changes in environmental carcinogenesis. © 201

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“…Of note, AhR activation, as triggered upon B[a]P exposure, appears to regulate the expression of several enzymes involved in energy metabolism; this cytosolic receptor is also known to interact with the F0F1ATPase (see[85] for review). In this context, how H + dynamics and AhR could act together to induce metabolic reprogramming upon B[a]P exposure remains an open question, as previously emphasized[4].…”

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confidence: 97%

Disturbances in H+ dynamics during environmental carcinogenesis

et al. 2019

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Abbreviations: B[a]P: benzo[a]pyrene; GPCR: G-protein coupled receptor; MCT: monocarboxylate transporter; NHE1: Na + /H + exchanger 1HIGHLIGHTS Benzo[a]pyrene, a well-known environmental carcinogen, alters H + dynamics. NHE1 activation by B[a]P plays a key role in H + dynamics alterations. B[a]P-altered pH controls cell death/survival balance via mitochondria and lysosome. ABSTRACTDespite the improvement of diagnostic methods and anticancer therapeutics, the human population is still facing an increasing incidence of several types of cancers. According to the World Health Organization, this growing trend would be partly linked to our environment, with around 20% of cancers stemming from exposure to environmental contaminants, notably chemicals like polycyclic aromatic hydrocarbons (PAHs). PAHs are widespread pollutants in our environment resulting from incomplete combustion or pyrolysis of organic material, and thus produced by both natural and anthropic sources; notably benzo[a]pyrene (B[a]P), i.e. the prototypical molecule of this family, that can be detected in cigarette smoke, diesel exhaust particles, occupational-related fumes, and grilled food. This molecule is a well-recognized carcinogen belonging to group 1 carcinogens. Indeed, it can target the different steps of the carcinogenic process and all cancer hallmarks. Interestingly, H + dynamics have been described as key parameters for the occurrence of several, if not all, of these hallmarks. However, information regarding the role of such parameters during environmental carcinogenesis is still very scarce. The present review will thus mainly give an overview of the impact of B[a]P on H + dynamics in liver cells, and will show how such alterations might impact different aspects related to the finely-tuned balance between cell death and survival processes, thereby likely favoring environmental carcinogenesis. In total, the main objective of this review is to encourage further research in this poorly explored field of environmental molecular toxicology.

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Environmental carcinogenesis and pH homeostasis: Not only a matter of dysregulated metabolism

Cited by 34 publications

References 217 publications

Mechanisms involved in the death of steatotic WIF-B9 hepatocytes co-exposed to benzo[a]pyrene and ethanol: a possible key role for xenobiotic metabolism and nitric oxide

Mechanisms involved in the death of steatotic WIF-B9 hepatocytes co-exposed to benzo[a]pyrene and ethanol: a possible key role for xenobiotic metabolism and nitric oxide

Nrf2 and AhR in metabolic reprogramming after contaminant exposure

Disturbances in H+ dynamics during environmental carcinogenesis

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