High throughput transcriptomic profiling of MCF10A cells exposed to breast cancer disparities associated chemicals
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220051 | GEO | 2024/04/10
REPOSITORIES: GEO
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Project description:Several epigenome-wide association studies (EWAS) have been shown to identify epigenetic alterations (i.e., epimutations) associated with diseases. The sperm epimutations potentially involved in the transgenerational inheritance of specific pathologies have been identified. Transgenerational sperm epimutations associated with kidney, prostate, puberty, testis, obesity, and multiple pathologies have been identified for a variety of environmental toxicants including dioxin, plastics, pesticides, glyphosate, methoxychlor, atrazine, and jet fuel. The transgenerational sperm epimutations for exposure and disease-specific epimutations have been identified in these EWAS studies. The current study used the information from these previous toxicant-induced epigenetic transgenerational inheritance EWAS rat studies and adds a comparable control group, rats that have not been exposed to any particular toxicant. Two additional control groups were collected and are presented here.
2022-04-27 | GSE198452 | GEO
Project description:Early life stages are generally most sensitive to toxic effects. Our knowledge on the action of man-made chemicals on the developing vertebrate embryo is, however, rather limited. We exposed zebrafish embryos to 11 of environmental toxicants and measured the changes in gene expression profiles by microarray. Our results demonstrate that the genome of the zebrafish embryo responds to toxicant exposure in a highly sensitive and specific manner. Keywords: toxicants response genes expression profiles
2008-01-03 | GSE9357 | GEO
Project description:The number and type of synthetic chemicals that are being produced worldwide continues to increase significantly. While these industrial chemicals provide numerous benefits, there is no doubt that some have potential to damage the environment and health. Toxicity must be evaluated and use must be carefully controlled and monitored in order to minimize potential damage. DNA microarray technology has become an important new technique in toxicology. We are using the yeast Saccharomyces cerevisiae as a model organism for toxicological study because it is a simple, fast-growing eukaryote that has been thoroughly characterized. In order to evaluate toxicity by newly synthesized or mixture chemicals, toxicity-induced gene expression alteration profiles by known chemicals should be collected. In our study, cells need to be exposed with same experimental cellular condition, semi lethal (IC50), respectively. In the case of lindane (gamma-hexachlorocyclohexane) (CAS; 58-89-9), the exposure dose was decided as 2 ppm by growth curve with continuously diluted exposure. Lindane is a organochlorine pesticides that is recognized as a carcinogen and suspected to be cardiovascular or blood toxicant, developmental toxicant, endocrine toxicant, gastrointestinal or liver toxicant, immunotoxicant, kidney toxicant, neurotoxicant, reproductive toxicant, respiratory toxicant and skin or sense organ toxicant. Keywords: stress response
2007-11-01 | GSE9358 | GEO
Project description:Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat. Rats were exposed to sub-chronic low doses of the Sertoli cell toxicant 2,5-hexanedione (HD) or water (control for HD) for 3 months. Some rats in each group underwent 3 months of post-exposure recovery.
2012-09-01 | E-GEOD-34641 | biostudies-arrayexpress
Project description:Various chemicals, including pesticides, heavy metals, and metabolites of tobacco, have been detected in fetal environment. Fetuses are exposed to these chemicals at relatively low concentrations; however, their risk of developing neurological and behavioral disorders increases after birth. We aimed to evaluate the effects of five chemicals (diethylphosphate, cotinine, octachlorodipropyl ether, mercury, and selenium) detected in the serum of pregnant mothers on DNA methylation status during neural development using human neural stem cells.
2023-12-06 | GSE235146 | GEO
Project description:<p>Exposure to synthetic and natural chemicals is a major environmental risk factor in the etiology of many chronic diseases. Investigating complex co-exposures is necessary for a holistic assessment in exposome-wide association studies. In this work, a sensitive liquid chromatography-tandem mass spectrometry approach was developed and validated. The assay enables the analysis of more than 80 highly-diverse xenobiotics in urine, serum/plasma and breast milk; with detection limits generally in the pg-ng mL-1 range. In plasma of extremely-premature infants, 27 xenobiotics are identified; including contamination with plasticizers, perfluorinated alkylated substances and parabens. In breast milk samples collected longitudinally over the first 211 days post-partum, 29 analytes are detected, including pyrrolizidine- and tropane alkaloids which have not been identified in this matrix before. A preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, we observe significant early-life co-exposure to multiple toxicants, and demonstrate the method's applicability for large-scale exposomics-type cohort studies.</p>
2023-10-26 | MTBLS2442 | MetaboLights
Project description:High throughput transcriptomic profiling of MCF10A cells exposed to breast cancer disparities associated chemicals
| PRJNA908115 | ENA
Project description:Pesticides are chemical compounds widely used in agriculture to control pests, since the 1960s. Regardless of its specific targets, such substances, unfortunately, can reach the human organism, and negative cumulative effects have been reported in people worldwide. Chronic exposure to pesticides has been discussed as a significant risk factor for the development of cancer, including breast tumors. Breast cancer is the most common malignant neoplasia that affects women worldwide, whose origin is mostly connected to life habits and the environment, and to a lesser extent to inheritable genetic mechanisms. Therefore, the contribution of substances as pesticides, that are present in the environment continuously, may have a pivotal role in the genesis breast cancer, especially in geographic areas in which women are important players in the rural work and are in direct contact with these compounds. In vitro and experimental studies have broadly reported the mechanisms triggered by pesticides that contribute to breast carcinogenesis, which fall essentially within DNA damage-based events in association with hormones deregulation and rising of metabolites that activate oncogenes (Alleva et al., 2018, BRADLOW et al., 1995). However, few is known about how these mechanisms are connected, as well as the manner that they can correlate with disease prognosis and clinicopathological features in human breast cancer as a result of the toxic consequences of pesticide exposure. In the last years, aiming to expand the knowledge about beyond isolated biological findings, high throughput molecular approaches combined with bioinformatics designs raised as powerful tools to understand breast cancer behavior and biology. Thereby, it was possible to broadcast that breast cancer is a very complex disease, and that distinct mechanisms are activated depending on specific clinicopathological characteristics. As far as we know, there are still no studies reporting the use of proteomics-based strategies to assess the impact of chronic pesticide exposure in women with breast cancer. To fill this gap, the present study proposes a toxicoproteomics perspective to investigate the systemic profile of differentially expressed proteins in the blood of breast cancer patients chronically exposed to pesticides, by using a high-throughput label-free proteomic strategy, and provide an integrative clinicopathological view based on bioinformatics approaches and validation experiments.
2021-09-09 | PXD018577 | Pride
Project description:We hypothesized that embryonic exposure to a mixture of chemicals (containing phenols, phthalates, pesticides, heavy metals, and perfluorinated, polychlorinated, and polybrominated compounds) identified as commonly found in the human amniotic fluid (as calculated in Fini et al., ) could lead to altered brain development. We assessed its effect on TH signaling and neuro-development in an amphibian model (Xenopus laevis) highly sensitive to thyroid disruption. Fertilized eggs were exposed for eight days to either TH (thyroxine, T4 10 nM) or the amniotic mixture (at the actual concentration) until reaching stage NF47, where we analyzed gene expres-sion in the brains of exposed tadpoles using both RT-qPCR and RNA sequencing.
2023-01-27 | GSE223829 | GEO
Project description:Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat.
2012-09-01 | GSE34641 | GEO