Oxidative stress, mutagenic effects, and cell death induced by retene

Peixoto, Milena Simões; Silva, Francisco Carlos da; Galvão, Marcos Felipe de Oliveira; Roubicek, Deborah A.; Alves, Nilmara de Oliveira; Medeiros, Sílvia Regina Batistuzzo de

doi:10.1016/j.chemosphere.2019.05.123

Cited by 27 publications

(17 citation statements)

References 75 publications

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“…At higher retene concentrations associated with teratogenicity, disruption of redox balance appears to play a key role in toxicity response. This is consistent with previous studies implicating oxidative stress in retene-induced toxicity ( Peixoto et al, 2019 ; Jiang et al, 2020 ). Whether effects of oxidative stress are responsible for retene-induced teratogenicity is still unclear, though the findings of this study support this hypothesis.…”

Section: Discussionsupporting

confidence: 94%

Concentration-response gene expression analysis in zebrafish reveals phenotypically-anchored transcriptional responses to retene

et al. 2022

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants and are associated with human disease. Canonically, many PAHs induce toxicity via activation of the aryl hydrocarbon receptor (AHR) pathway. While the interaction between PAHs and the AHR is well-established, understanding which AHR-regulated transcriptional effects directly result in observable phenotypes and which are adaptive or benign is important to better understand PAH toxicity. Retene is a frequently detected PAH in environmental sampling and has been associated with AHR2-dependent developmental toxicity in zebrafish, though its mechanism of toxicity has not been fully elucidated. To interrogate transcriptional changes causally associated with retene toxicity, we conducted whole-animal RNA sequencing at 48 h post-fertilization after exposure to eight retene concentrations. We aimed to identify the most sensitive transcriptomic responses and to determine whether this approach could uncover gene sets uniquely differentially expressed at concentrations which induce a phenotype. We identified a concentration-response relationship for differential gene expression in both number of differentially expressed genes (DEGs) and magnitude of expression change. Elevated expression of cyp1a at retene concentrations below the threshold for teratogenicity suggested that while cyp1a expression is a sensitive biomarker of AHR activation, it may be too sensitive to serve as a biomarker of teratogenicity. Genes differentially expressed at only non-teratogenic concentrations were enriched for transforming growth factor-β (TGF-β) signaling pathway disruption while DEGs identified at only teratogenic concentrations were significantly enriched for response to xenobiotic stimulus and reduction-oxidation reaction activity. DEGs which spanned both non-teratogenic and teratogenic concentrations showed similar disrupted biological processes to those unique to teratogenic concentrations, indicating these processes were disrupted at low exposure concentrations. Gene co-expression network analysis identified several gene modules, including those associated with PAHs and AHR2 activation. One, Module 7, was strongly enriched for AHR2-associated genes and contained the strongest responses to retene. Benchmark concentration (BMC) of Module seven genes identified a median BMC of 7.5 µM, nearly the highest retene concentration with no associated teratogenicity, supporting the hypothesis that Module seven genes are largely responsible for retene toxicity.

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Section: Discussionsupporting

confidence: 94%

Concentration-response gene expression analysis in zebrafish reveals phenotypically-anchored transcriptional responses to retene

et al. 2022

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“…Retene is known to induce oxidative stress and DNA damage (Maria et al, 2005;Peixoto et al, 2019). In the present study, retene was the only PAH to significantly induce the superoxide dismutase protein in the cardiac tissue, probably as a response to an increased content in reactive oxygen species (ROS).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 62%

Retene, pyrene and phenanthrene cause distinct molecular-level changes in the cardiac tissue of rainbow trout (Oncorhynchus mykiss) larvae, part 2 – Proteomics and metabolomics

Rigaud

Eriksson

Rokka

et al. 2020

Science of The Total Environment

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“…P53 is a tumor suppressor that monitors the cell cycle, maintains genomic stability by participating in DNA repair and is coexpressed with angiogenic genes such as Smad4 to inhibit tumor angiogenesis (40,41). FoxO is a nuclear protein subfamily that mediates the inhibition of insulin or insulin-like growth factor to further influence cell cycle regulation, energy metabolism, protein stability, oxidative stress, apoptosis, and immunity (42,43).…”

Section: Discussionmentioning

confidence: 99%

A prognostic nomogram for lung adenocarcinoma based on immune-infiltrating Treg-related genes: from bench to bedside

Wang¹,

Xiao²,

Gong³

et al. 2021

Transl Lung Cancer Res

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Background: Accumulating evidence suggests that lymphocyte infiltration in the tumor microenvironment is positively correlated with tumorigenesis and development, while the role of Tregs (regulatory T cells) has been controversial. Therefore, we attempted to discover the possible value of Tregs for lung adenocarcinoma (LUAD). Methods:The gene-sequencing data of LUAD were applied from three Gene Expression Omnibus (GEO) datasets-GSE10072, GSE32863 and GSE43458; the corresponding fractions of tumor-infiltrating immune cells were extracted from the CIBERSORTx portal. Weighted gene coexpression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were conducted to identify the significant module and candidate genes related to Tregs. The role of candidate genes in LUAD was further verified using data from The Cancer Genome Atlas (TCGA) database. Finally, we constructed a nomogram model to predict the prognosis of LUAD by plotting Kaplan-Meier (K-M), receiver operating characteristic (ROC) and calibration curves, which elucidated the performance of the nomogram.Results: In total, 10,047 genes in 333 samples (196 tumor and 137 normal samples) from the GEO database were included. By WGCNA and PPI analysis, we identified a significant black module and 36 candidate genes related to Treg. Next, the candidate genes were verified using TCGA data by Cox regression analysis to screen 13 hub genes that stratified LUAD patients into low-or high-risk groups. Low-risk patients showed a significantly longer overall survival (OS) than high-risk patients (3-year OS: 70.2% vs. 35.2%; 5-year OS: 36.6% vs. 0; P=1.651E-09), and the areas under the ROC curves (AUCs) showed good (3year AUC: 0.733; 5-year AUC: 0.777). Next, we constructed a survival nomogram combining the hub genes and clinical parameters; the low-risk patients still showed a favorable prognosis compared with that of the high-risk patients (P=7.073E-13), and the AUCs were better (3-year AUC: 0.763; 5-year AUC: 0.873). Conclusions:We revealed the role of immune-infiltrating Treg-related genes in LUAD and constructed a prognostic nomogram, which may help clinicians make optimal therapeutic decisions and help patients obtain better outcomes.

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Oxidative stress, mutagenic effects, and cell death induced by retene

Cited by 27 publications

References 75 publications

Concentration-response gene expression analysis in zebrafish reveals phenotypically-anchored transcriptional responses to retene

Concentration-response gene expression analysis in zebrafish reveals phenotypically-anchored transcriptional responses to retene

Retene, pyrene and phenanthrene cause distinct molecular-level changes in the cardiac tissue of rainbow trout (Oncorhynchus mykiss) larvae, part 2 – Proteomics and metabolomics

A prognostic nomogram for lung adenocarcinoma based on immune-infiltrating Treg-related genes: from bench to bedside

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