Benzo[a]pyrene activates an AhR/Src/ERK axis that contributes to CYP1A1 induction and stable DNA adducts formation in lung cells

Vázquez‐Gómez, Gerardo; Rocha‐Zavaleta, Leticia; Rodrı́guez-Sosa, Miriam; Petrosyan, Pavel; Rubio-Lightbourn, Julieta

doi:10.1016/j.toxlet.2018.03.012

Cited by 33 publications

(27 citation statements)

References 55 publications

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“…The AhR/CYP1A1 pathway participates in carcinogenesis by mediating stem properties, the formation of mammospheres, expansion of breast cancer stem cells, and the transcriptional activity of AhR is mainly implicated in such effects (24). Our study also reveals that GPR30 participates and favors AhR-dependent transcriptional activity in early-transformed breast cells.…”

Section: Discussionsupporting

confidence: 57%

“…These latter are involved in the metabolic activation of B[a]P in genotoxic metabolites forming DNA adducts relevant for carcinogenesis [for review, ( 21 , 22 )]. A growing body of evidence is accumulating implicating the B[a]P/AhR/CYP1A1 pathway in carcinogenesis ( 23 – 25 ). At early stages of carcinogenesis, short-term and millimolar B[a]P doses were shown to induce aggressiveness and transformation of non-cancerous human mammary epithelial cells ( 26 – 28 ).…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

et al. 2020

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

et al. 2020

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“…Dietary flavonoids possess a number of functions that include but not limited to anti‐inflammatory, antiallergic, antibacterial, and antimutagenic properties . The initial step of B(a)P induced lung toxicity and injury is the activation of the aryl hydrocarbon receptor leading to transcription of genes including cytochrome P450 1A1 (CYP1A1) and subsequent generation of reactive oxygen species (ROS), and the formation of DNA adduct that is capable of causing DNA mutation ultimately leads to lung tumorigenesis . Excessive formation of free radicals can react with the membrane lipid causing its damage.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Diosmin against benzo(a)pyrene‐induced lung injury in Swiss Albino Mice

Islam

Shree

Afzal

et al. 2020

Environmental Toxicology

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Diosmin, a naturally occurring flavonoid commonly present in citrus fruit, is known to exhibit anti-inflammatory, antimutagenic, antioxidant, and free radical scavenging as well as blood lipid lowering activities among others. Diosmin has also been used for the treatment of various diseases including diabetes mellitus and Alzheimer's disease. Our study explores the role of Diosmin in pulmonary toxicity (lung injury) induced by environmental contaminant benzo(a)pyrene [B(a)P]. Swiss Albino Mice (SAM) were administered with either Diosmin 100 or 200 mg/kg body weight daily for 14 days and then challenged with a single dose of B(a)P. On the 15th day, animals were sacrificed; lung tissues and blood were collected for molecular analysis. B(a)P administration in mice induced the thickening of lung epithelium, damaged alveolar architecture, and promoted inflammatory cell infiltration in the lung tissues. Also, B[a]P significantly increased the expression of NF-kB, COX-2, IL-6, Bax, cleaved caspase 3, and cleaved PARP proteins and decreased antioxidant enzyme levels. Diosmin-100 and Diosmin-200 significantly attenuated the damage to lung epithelium, alveolar architecture, and reduced inflammatory cell infiltration in the lung tissues of mice. Diosmin significantly (P < .05) attenuated the levels of oxidative stress markers: lactate dehydrogenase and xanthine oxidase. A decrease in expression of NF-kB, COX-2, IL-6, Bax, cleaved caspase 3, and cleaved PARP proteins in mice was challenged with B[a]P. Diosmin thus could be a promising therapeutic adjuvant against B[a]Pinduced oxidative stress and lung damage. K E Y W O R D S benzo(a)pyrene, diosmin, inflammation, lung injury, oxidative stress, pulmonary toxicity

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“…Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the atmosphere as persistent contaminants, and almost all of PAHs exhibit high aryl hydrocarbon receptor (AhR) binding affinity (K. H. Kim, Jahan, Kabir, & Brown, 2013; Tian et al, 2015). Benzo(a)pyrene (B[a]P), the major carcinogenic PAH, is listed as a group I human carcinogen by the International Agency for Research on Cancer (IARC; IARC, 2012; Vázquez‐Gómez, Rocha‐Zavaleta, Rodríguez‐Sosa, & Petrosyan, 2018). Although B[a]P shows no genotoxicity, it can be metabolized by xenobiotic‐metabolizing cytochrome P450 (CYP450) to the final metabolite, benzo[a]pyrene‐ trans ‐7,8‐dihydrodiol‐9,10‐epoxide (B[a]PDE), which covalently binds to macromolecules and forms mutagenic DNA adducts, then inhibits DNA synthesis, inducing cell cycle arrest (Shiizaki, Kawanishi, & Yagi, 2013; Wei et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

6‐Formylindolo[3,2‐b]carbazole reduces apoptosis induced by benzo[a]pyrene in a mitochondrial‐dependent manner

Gan

Ding

Chen

2020

Cell Biology International

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Benzo[a]pyrene (B[a]P), a potent carcinogen, has been proved that it can induce apoptosis via activation of the aryl hydrocarbon receptor (AhR) pathway. The metabolite of tryptophan 6‐formylindolo[3,2‐b]carbazole (FICZ), an endogenous activator of AhR, plays bifunctional roles in cell growth and apoptosis. However, whether and how FICZ can reduce the toxicity of B[a]P and the mechanism underlying this remain unclear. In this study, FICZ interfered with the toxicity of B[a]P in mouse hepatocarcinoma cell line Hepa1‐6. The results of the MTT assay indicated that FICZ and B[a]P made opposite effects on cell proliferation. The scratch‐wound healing assay showed that B[a]P (1 µM for 24 hr) exposure triggered cell migration and that was inhibited by FICZ (10 nM). In addition, FICZ ameliorated B[a]P‐induced apoptosis by inhibiting reactive oxygen species generation and caspase‐3 activation, as well as increasing reduced glutathione level in mitochondria. Furthermore, gene expression analyses indicated that FICZ competed with B[a]P, which reduced the transcriptional activation of the cyp1a1 and cyp1b1 genes, as well as Bcl2 and P53. Accordingly, the interaction between FICZ and B[a]P in the AhR pathway inhibited apoptosis in a mitochondrial‐dependent manner, suggesting that endogenous compound may reduce the toxicity of exogenous pollutant in vivo and providing an available way to improve health condition related to the hepatic metabolic disorder.

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Benzo[a]pyrene activates an AhR/Src/ERK axis that contributes to CYP1A1 induction and stable DNA adducts formation in lung cells

Cited by 33 publications

References 55 publications

Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

Long-Term Exposure of Early-Transformed Human Mammary Cells to Low Doses of Benzo[a]pyrene and/or Bisphenol A Enhances Their Cancerous Phenotype via an AhR/GPR30 Interplay

Protective effect of Diosmin against benzo(a)pyrene‐induced lung injury in Swiss Albino Mice

6‐Formylindolo[3,2‐b]carbazole reduces apoptosis induced by benzo[a]pyrene in a mitochondrial‐dependent manner

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