Dataset Information

Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

ABSTRACT: To reduce reliance on long-term in vivo studies, short-term data linking early molecular-based measurements to later adverse health effects is needed. Although transcriptional-based benchmark dose (BMD_T) modeling has been used to estimate potencies and stratify chemicals based on potential to induce later-life effects, dose-responsive epigenetic alterations have not been routinely considered. Here, we evaluated the utility of microRNA (miRNA) profiling in mouse liver and blood, as well as in mouse primary hepatocytes in vitro, to indicate mechanisms of liver perturbation due to short-term exposure of the known rodent liver hepatotoxicant and carcinogen, furan. Benchmark dose modeling of miRNA measurements (BMD_miR) were compared to the referent transcriptional (BMD_T) and apical (BMD_A) estimates. These analyses indicate a robust dose response for 34 miRNAs to furan and involvement of p53-linked pathways in furan-mediated hepatotoxicity, supporting mRNA and apical measurements. Liver-sourced miRNAs were also altered in the blood and primary hepatocytes. Overall, these results indicate mechanistic involvement of miRNA in furan carcinogenicity and provide evidence of their potential utility as accessible biomarkers of exposure and disease.

SUBMITTER: Nelson GM

PROVIDER: S-EPMC10530563 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

Nelson Gail M GM Carswell Gleta K GK Swartz Carol D CD Recio Leslie L Yauk Carole L CL Chorley Brian N BN

Toxicology letters 20230728

To reduce reliance on long-term in vivo studies, short-term data linking early molecular-based measurements to later adverse health effects is needed. Although transcriptional-based benchmark dose (BMD<sub>T</sub>) modeling has been used to estimate potencies and stratify chemicals based on potential to induce later-life effects, dose-responsive epigenetic alterations have not been routinely considered. Here, we evaluated the utility of microRNA (miRNA) profiling in mouse liver and blood, as wel ...[more]

PMID: 37517673

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Project description:A dataset range of isocenter congruency verification tests have been examined from a statistical perspective for the purpose of establishing tolerance levels that are meaningful, based on the fundamental limitation of linear accelerator isocentricity and the demands of a high-precision stereotactic radiosurgery program. Using a laser-defined isocenter, a total of 149 individual isocenter congruency tests were examined with recorded values for ideal spatial corrections to the isocenter test tool. These spatial corrections were determined from radiation exposures recorded on an electronic portal imaging device (EPID) at various gantry, collimator, and treatment couch combinations. The limitations of establishing an ideal isocenter were quantified from each variable which contributed to uncertainty in isocenter definition. Individual contributors to uncertainty, specifically, daily positioning setup errors, gantry sag, multileaf collimator (MLC) offset, and couch walkout, were isolated from isocenter congruency measurements to determine a clinically meaningful isocenter measurement. Variations in positioning of the test tool constituted, on average, 0.38 mm magnitude of correction. Gantry sag and MLC offset contributed 0.4 and 0.16 mm, respectively. Couch walkout had an average degrading effect to isocenter of 0.72 mm. Considering the magnitude of uncertainty contributed by each uncertainty variable and the nature of their combination, an appropriate schedule action and immediate action level were determined for use in analyzing daily isocenter congruency test results in a stereotactic radiosurgery (SRS) program. The recommendations of this study for this linear accelerator include a schedule action level of 1.25 mm and an immediate action level of 1.50mm, requiring prompt correction response from clinical medical physicists before SRS or stereotactic body radiosurgery (SBRT) is administered. These absolute values were derived from considering relative data from a specific linear accelerator and, therefore, represent a means by which a numerical quantity can be used as a test threshold with relative specificity to a particular linear accelerator.

Dataset Information

Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

Publications

Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

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