Project description:Transcriptional profiling of mouse liver after short-term in vivo exposure (up to 56 days) of C57BL-mice to carcinogenic and non-carcinogenic chemicals
Project description:Many innovative techniques and scientific improvements are available to tackle societal concerns, like public health safety and confining the risk of cancerous exposure to chemicals, but have not been thoroughly tested and implicated yet. We investigated if microRNA and mRNA transcription profiles can be implemented in a short-term carcinogen classifier assay. Our study is additionally focusing on the drawbacks of present-day carcinogen screening strategies and also aims to contribute to a more ethical approach towards animal use and welfare within risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment. [mRNA profling] 96 hepatic samples in total, 8 control untreated samples, replicates per treated group n=4-6
Project description:Many innovative techniques and scientific improvements are available to tackle societal concerns, like public health safety and confining the risk of cancerous exposure to chemicals, but have not been thoroughly tested and implicated yet. We investigated if microRNA and mRNA transcription profiles can be implemented in a short-term carcinogen classifier assay. Our study is additionally focusing on the drawbacks of present-day carcinogen screening strategies and also aims to contribute to a more ethical approach towards animal use and welfare within risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment.
Project description:Many innovative techniques and scientific improvements are available to tackle societal concerns, like public health safety and confining the risk of cancerous exposure to chemicals, but have not been thoroughly tested and implicated yet. We investigated if microRNA and mRNA transcription profiles can be implemented in a short-term carcinogen classifier assay. Our study is additionally focusing on the drawbacks of present-day carcinogen screening strategies and also aims to contribute to a more ethical approach towards animal use and welfare within risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mRNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment. [microRNA profling] 68 hepatic samples in total, 3 control untreated samples, replicates per treated group n=3-4
Project description:Many innovative techniques and scientific improvements are available to tackle societal concerns, like public health safety and confining the risk of cancerous exposure to chemicals, but have not been thoroughly tested and implicated yet. We investigated if microRNA and mRNA transcription profiles can be implemented in a short-term carcinogen classifier assay. Our study is additionally focusing on the drawbacks of present-day carcinogen screening strategies and also aims to contribute to a more ethical approach towards animal use and welfare within risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mRNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment.
Project description:Trancriptional profiling of rat liver after short-term (up tp 14 days) administration of carcinogenic and non-carcinogenic chemicals
Project description:The environment outside the Earth’s protective magnetosphere is a much more threatening and complex space environment. The dominant causes for radiation exposure, solar particle events and galactic cosmic rays, contain high-energy protons. In space, astronauts need healthy and highly functioning cognitive abilities, of which the hippocampus plays a key role. Therefore, understanding the effects of 1H exposure on hippocampal-dependent cognition is vital for de-veloping mitigative strategies and protective countermeasures for future missions. To investi-gate these effects, we subjected 6-month-old female CD1 mice to 0.75 Gy fractionated 1H (250 MeV) whole-body irradiation at the NASA Space Radiation Laboratory. The cognitive perfor-mance of the mice was tested 3 months after irradiation using Y-maze and morris water maze tests. Both sham-irradiated and 1H-irradiated mice significantly preferred exploration of the novel arm compared to the familiar and start arms, indicating intact spatial and short-term memory. Both groups statistically spent more time in the target quadrant, indicating spatial memory retention. There were no significant differences in neurogenic and gliogenic cell counts after irradiation. In addition, proteomic analysis revealed no significant upregulation or down-regulation of proteins related to behavior, neurological disease, or neural morphology. Our data suggests 1H exposure does not impair hippocampal-dependent spatial or short-term memory in female mice.
Project description:The Iconix data set (endpoint B) was provided by Iconix Biosciences, Inc. (Mountain View, CA, USA). The study objective was to assess, upon short term exposure, hepatic tumor induction bynon-genotoxic chemicals, since there are currently no accurate and well-validated short-term tests to identify non-genotoxic hepatic tumorigens, thus necessitating an expensive 2-year rodent bioassay before a risk assessment can begin. The reanalysis has been carried out with log2 transformed gene expression levels of the raw signal values. The data in this Series were initially submitted in GEO Series GSE8251.
Project description:The increasing number of man-made chemicals in the environment that may pose a carcinogenic risk emphasizes the need for the development of reliable time- and cost-effective approaches for carcinogen detection. To address this issue, we have investigated the utility of human hepatocytes for the in vitro identification of genotoxic and non-genotoxic carcinogens. Induced pluripotent stem cell (iPSC)-derived human hepatocytes were treated with the genotoxic carcinogens aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P) and with the non-genotoxic liver carcinogen methapyrilene at non-cytotoxic concentrations for 7 days, and transcriptomic profile was examined. 1569 (892 protein-coding and 677 non-coding), 1693 (922 protein-coding and 771 non-coding), and 2061 (1462 protein-coding and 599 non-coding) differentially expressed genes were detected in cells treated with AFB1, B[a]P, and methapyrilene, respectively. Additionally, we examined the toxicogenomics response to AFB1, B[a]P, and methapyrilene exposure in human HepaRG cells and demonstrated that carcinogens had a less prominent effect on the cellular transcriptome as compared to that in human iPSC-derived hepatocytes. Overall, the results demonstrate that the prime non-genotoxic effect of exposure to carcinogens, regardless of their mode of action, in short-term in vitro testing is a profound global transcriptome response, indicating a greater value of toxicogenomics for rapid carcinogen screening in vitro.