Molecular effects of arsenic and smokeless tobacco aqueous extract in cultured cells [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1123234 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29380832.fastq.gz | Fastqsanger.gz | |||
| SRR29380833.fastq.gz | Fastqsanger.gz | |||
| SRR29380834.fastq.gz | Fastqsanger.gz | |||
| SRR29380835.fastq.gz | Fastqsanger.gz | |||
| SRR29380836.fastq.gz | Fastqsanger.gz |
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Project description:Molecular effects of arsenic and smokeless tobacco aqueous extract in cultured cells
| PRJNA1120110 | ENA
Project description:Chronic arsenic exposure can lead to various health issues including cancer. There has been a growing concern about co-exposure to various prevalent lifestyle habits and their role in the enhancement of arsenic toxicity. Smokeless tobacco (SLT) products are extensively consumed in many South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the oral epithelial cell responses to arsenic and SLT alone and in co-exposure, we performed multi-omics analyses of DNA methylome, transcriptomic reprogramming and genotoxic effects in controlled experimental settings. Chronic exposure studies revealed hypomethylation of genes involved in inflammation response and apoptosis, further corroborated by the upregulation of genes involved in these processes due to arsenic and the combined treatment in acute exposure setting. Next, to validate the omics results at the phenotypic level, we observed a dose dependent decrease in cell viability, induction of DNA damage, cell cycle changes, and an increase in apoptotic cells, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. The observed DNA damage was likely the result of apoptosis induction, as chronic exposure experiments based on whole-exome sequencing did not reveal increased mutagenicity following the arsenic and/or SLT exposure. Our integrative omics study provides insights into both chronic and acute responses to arsenic and SLT co-exposure, with both types of responses converging on some of the same mechanisms. We identified large-scale epigenomic and transcriptomic reprograming associated with arsenic and SLT co-exposure, alongside genotoxic effects presumably manifesting as consequences of apoptosis induction. The findings point to a role of arsenic and SLT in altering key molecular responses, especially in the context of the co-exposure, and call for further studies in humans in the areas of exposure, to validate the observed mechanisms.
2024-12-04 | GSE269103 | GEO
Project description:Chronic arsenic exposure can lead to various health issues including cancer. There has been a growing concern about co-exposure to various prevalent lifestyle habits and their role in the enhancement of arsenic toxicity. Smokeless tobacco (SLT) products are extensively consumed in many South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the oral epithelial cell responses to arsenic and SLT alone and in co-exposure, we performed multi-omics analyses of DNA methylome, transcriptomic reprogramming and genotoxic effects in controlled experimental settings. Chronic exposure studies revealed hypomethylation of genes involved in inflammation response and apoptosis, further corroborated by the upregulation of genes involved in these processes due to arsenic and the combined treatment in acute exposure setting. Next, to validate the omics results at the phenotypic level, we observed a dose dependent decrease in cell viability, induction of DNA damage, cell cycle changes, and an increase in apoptotic cells, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. The observed DNA damage was likely the result of apoptosis induction, as chronic exposure experiments based on whole-exome sequencing did not reveal increased mutagenicity following the arsenic and/or SLT exposure. Our integrative omics study provides insights into both chronic and acute responses to arsenic and SLT co-exposure, with both types of responses converging on some of the same mechanisms. We identified large-scale epigenomic and transcriptomic reprograming associated with arsenic and SLT co-exposure, alongside genotoxic effects presumably manifesting as consequences of apoptosis induction. The findings point to a role of arsenic and SLT in altering key molecular responses, especially in the context of the co-exposure, and call for further studies in humans in the areas of exposure, to validate the observed mechanisms.
2024-12-04 | GSE269688 | GEO
Project description:The current study was performed for analysis of the biological effects of vapor from novel tobacco vapor product in comparison with 3R4F cigarette smoke. This study was performed using a three-dimensional culture system composed of an air-liquid interface culture of primary normal human bronchial epithelial cells (MucilAir). The MucilAir tissues were subjected to 17 days of exposure to the aqueous extract of novel tobacco product vapor or 3R4F cigarette smoke. The number of differentially expressed genes increased in MucilAir tissues exposed to aqueous extract of each test product dependent on exposure duration. The number of differentially expressed genes was lower in the tissues exposed to aqueous extract of novel tobacco product vapor compared to the tissues exposed to aqueous extract of 3R4F cigarette smoke.
2020-04-15 | E-MTAB-8920 | biostudies-arrayexpress
Project description:Objectives: The aim of this study was to investigate the salivary proteomic profile of smokeless tobacco users in comparison to non-smokers using LC-MS/MS and to investigate the biological changes associated with smokeless tobacco use and oral cancer. Materials & Methods: Saliva samples of 65 participants were collected and divided into three groups: control (25 participants) , smokeless tobacco users group (25 participant), and oral cancer group (15 participant). The mean ages of the control participants, smokeless tobacco users, and oral cancer patients were 37.08 years, 37.8 years, and 52 years, respectively. The saliva samples were then prepared for LC-MS/MS analysis through in-solution digestion. The raw data files were processed using MaxQuant 2.1.0.0 with the human canonical proteome database. Results: The analysis revealed that 343 protein groups exhibited significantly altered abundance in the saliva samples. Among these, 43 out of 51 dysregulated proteins in the smokeless tobacco group were also dysregulated in the oral cancer group. Notably, Apolipoprotein A1 (ApoA1) and Pon1 were found to be significantly increased in both smokeless tobacco users and oral cancer patients. Furthermore, six out of the 20 most significantly altered proteins were mitochondrial proteins, and all of them were decreased relative to controls in both smokeless tobacco users and cancer samples.
2025-11-17 | PXD045926 | Pride
Project description:Cigarette smoke causes diseases such as cardiovascular disorders. Heating tobacco, instead of burning, reduces consistently the amount of toxic compounds and may exert a reduced impact on cardiovascular health compared to cigarettes. Aqueous extract from the aerosol of a potential modified risk tobacco product, the carbon-heated tobacco product (CHTP) 1.2 was assessed in vitro for its impact, compared with a reference cigarette (3R4F), on a key mechanism of atherosclerosis, the adhesion of monocytic cells to artery endothelial cells. Human coronary arterial endothelial cells (HCAECs) were treated for 4h with conditioned media from monocytic Mono Mac-6 (MM6) cells exposed to the aqueous aerosol/smoke extracts for 2h (Indirect exposure) or directly with those extracts freshly generated (Fresh Direct exposure). Using a previously established in vitro adhesion assay design, MM6-HCAEC adhesion combined with inflammatory, oxidative stress, cytotoxicity and cell death markers was measured. The 3R4F extract promoted the adhesion of MM6 cells to HCAECs via distinct inflammatory- and cytotoxicity-driven mechanisms. In conclusions, our systems toxicology study demonstrated that approximately 10-15-fold higher concentrations of the CHTP1.2 aerosol extract were needed to elicit similar effects as the 3R4F smoke extract on cardiovascular disease-relevant inflammation and cytotoxicity-related mechanisms and markers investigated in vitro.
2018-08-09 | E-MTAB-6721 | biostudies-arrayexpress
Project description:Tobacco in its smoke and smokeless form are major risk factors for ESCC (esophageal squamous cell carcinoma). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in-vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over eight month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed that established cancer stem cell markers are elevated in tobacco treated cells. Decreased expression of enzymes associated with the glycolytic pathway and increased expression of a large number of mitochondrially localized proteins involved in the electron transport chain as well as enzymes of TCA cycle were also identified. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we hypothesise that chronic treatment of esophageal epithelial cells with tobacco leads to a cancer stem cell-like phenotype. These cells also show characteristic OXPHOS phenotype which can be potentially targeted as a therapeutic strategy.
2019-11-11 | PXD013396 | Pride
Project description:Specific recognition and bacterial adhesion to host cells by uropathogenic E. coli (UPEC) are the first steps towards infection of epithelial tissue of the human urogenital system. Therefore, targeting of UPEC virulence factors, relevant for adhesion, is a promising approach for prevention of recurrent urinary tract infections (UTI). A fully characterized plant-derived aqueous extract from the leaves of Orthosiphon stamineus (OWE), a plant traditionally used in clinical practice in Europe and Asia for UTI, has been shown to exert strong antiadhesive effects under in vitro and in vivo conditions. For improved understanding of the underlying mechanisms transcriptome analysis of OWE-treated UPEC strain UTI89 by Illumina sequencing and cross-validation of these data by qPCR indicated significant down-regulation of bacterial adhesins (curli, type 1-, F1C- and P fimbriae) and of the chaperone-mediated protein folding/unfolding and pilus assembly process; in contrast flagellar and motility-related genes were upregulated. We conclude that OWE transforms the sessile lifestyle of bacteria into a motile one and therefore disables bacterial attachment to the host cell. Additionally, the extract inhibited gene expression of multiple iron acquisition systems (Ent, Fep, Feo, Fhu, Chu, Sit, Ybt) concomitant with an upregulated expression of the ferric uptake regulator (Fur) repressor. The present study explains the antiadhesive and antiinfective effect of the plant extract by pinpointing specific biochemical and molecular targets.
2019-05-18 | GSE131382 | GEO
Project description:The practice of using chewing tobacco is common in certain socio-economic sections of southern Asia particularly in the Indian subcontinent. The molecular mechanism of smokeless tobacco which leads to malignancy is unclear. Chewing tobacco demonstrates a carcinogenic effect through chronic and not acute exposures. Using a cell line model, we studied the chronic effects of chewing tobacco on the proteome in normal oral keratinocytes (OKF6/TERT1). We carried out iTRAQ-based quantitative proteomic analysis of the untreated and chewing tobacco treated oral keratinocytes. LC-MS/MS analysis of this cell line pair resulted in the identification of 3,638 proteins of which 408 were found to be differentially expressed.
2016-12-14 | PXD001554 | Pride