Metabolomics insights for acquired platinum chemoresistance of A549 cells induced by chronic arsenic exposure
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Yang Zhou
PROVIDER: PXD044474 | iProX | Wed Aug 09 00:00:00 BST 2023
REPOSITORIES: iProX
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Project description:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Keywords: dose response
2007-11-17 | GSE9630 | GEO
Project description:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Keywords: dose response
2008-08-01 | GSE11056 | GEO
Project description:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Experiment Overall Design: Male C57BL/6 mice, fed on two commercially available laboratory diets (LRD-5001 and AIN-76A), were chronically exposed through drinking water or food, to environmentally relevant concentrations of sodium arsenite. Another group animals, fed on the AIN 76A diet, was IP injected with dexamethasone (1 mg/kg), sodium arsenite (1mg/kg), both dexamethosone and arsenite, or saline alone.
2008-10-21 | E-GEOD-11056 | biostudies-arrayexpress
Project description:Purpose: To determine the effects of sodium arsenite in male mice on adaptive thermogenesis. Methods: Male C57BL/6J mice were exposed to sodium arsenite in drinking water at 300 parts per billion (ppb) for 9 weeks Findings: Arsenic-treated mice experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass, and unilocular lipid droplet size in both subcutaneous inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT). Conclusion: Chronic arsenic exposure impacts the mitochondria of thermogenic tissues involved in energy expenditure and glucose regulation, providing novel mechanistic evidence for arsenic’s role in metabolic pathologies.
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Project description:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with; chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows,; but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Experiment Overall Design: Male C57BL/6 mice, fed on two commercially available laboratory diets (LRD-5001 and AIN-76A), were chronically exposed through drinking water or food, to environmentally relevant concentrations of sodium arsenite. Experiment Overall Design: Another group animals, fed on the AIN 76A diet, was IP injected with dexamethasone (1 mg/kg), sodium arsenite (1mg/kg), both dexamethosone and arsenite, or saline alone.
2008-06-16 | E-GEOD-9630 | biostudies-arrayexpress
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: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.
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Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation. A total of eight (8) samples with two biological replicates under four separate conditions: wild-type treated with deionized H2O for 36 days (NT); chronic low-dose arsenic exposure of 1 uM of sodium arsenite (iAs-T) for 36 days; chronic arsenic exposure of 1 uM of sodium arsenite for 26 days followed by removal of sodium arsenite for 10 days, measured at day 36 (iAs-Rev); and chronic arsenic exposure of 1 uM of sodium arsenite for 26 days, followed by removal of sodium arsenite exposure for 10 days, followed by 1 uM of chronic sodium arsenite exposure for 10 days (measured at day 46) (iAs-Rev-T).
2015-05-05 | E-GEOD-60760 | biostudies-arrayexpress