Steven M. Bryce
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View article: Visualization strategies to aid interpretation of <scp>high‐dimensional</scp> genotoxicity data
Visualization strategies to aid interpretation of <span>high‐dimensional</span> genotoxicity data Open
This article describes a range of high‐dimensional data visualization strategies that we have explored for their ability to complement machine learning algorithm predictions derived from MultiFlow® assay results. For this exercise, we focu…
View article: In vitro human cell‐based aneugen molecular mechanism assay
In vitro human cell‐based aneugen molecular mechanism assay Open
This laboratory previously described an in vitro human cell‐based assay and data analysis scheme that discriminates common molecular targets responsible for chemical‐induced in vitro aneugenicity: tubulin destabilization, tubulin stabiliza…
View article: Biomarkers of DNA damage response improve <i>in vitro</i> micronucleus assays by revealing genotoxic mode of action and reducing the occurrence of irrelevant positive results
Biomarkers of DNA damage response improve <i>in vitro</i> micronucleus assays by revealing genotoxic mode of action and reducing the occurrence of irrelevant positive results Open
We have previously described two flow cytometry-based in vitro genotoxicity tests: micronucleus (MN) scoring (MicroFlow®) and a multiplexed DNA damage response biomarker assay (MultiFlow®). Here, we describe a strategy for combining the as…
View article: Kinetics of γH2AX and phospho-histone H3 following pulse treatment of TK6 cells provides insights into clastogenic activity
Kinetics of γH2AX and phospho-histone H3 following pulse treatment of TK6 cells provides insights into clastogenic activity Open
The desire for in vitro genotoxicity assays to provide higher information content, especially regarding chemicals’ predominant genotoxic mode of action, has led to the development of a novel multiplexed assay available under the trade name…
View article: The use of benchmark dose uncertainty measurements for robust comparative potency analyses
The use of benchmark dose uncertainty measurements for robust comparative potency analyses Open
The Benchmark Dose (BMD) method is the favored approach for quantitative dose–response analysis where uncertainty measurements are delineated between the upper (BMDU) and lower (BMDL) confidence bounds, or confidence intervals (CIs). Littl…
View article: 3Rs‐friendly approach to exogenous metabolic activation that supports high‐throughput genetic toxicology testing
3Rs‐friendly approach to exogenous metabolic activation that supports high‐throughput genetic toxicology testing Open
MultiFlow® DNA Damage—p53, γH2AX, Phospho‐Histone H3 is a miniaturized, flow cytometry‐based assay that provides genotoxic mode of action information by distinguishing clastogens, aneugens, and nongenotoxicants. Work to date has focused on…
View article: Benchmark Dose Analysis of DNA Damage Biomarker Responses Provides Compound Potency and Adverse Outcome Pathway Information for the Topoisomerase II Inhibitor Class of Compounds
Benchmark Dose Analysis of DNA Damage Biomarker Responses Provides Compound Potency and Adverse Outcome Pathway Information for the Topoisomerase II Inhibitor Class of Compounds Open
Genetic toxicology data have traditionally been utilized for hazard identification to provide a binary call for a compound's risk. Recent advances in the scientific field, especially with the development of high‐throughput methods to quant…
View article: Evidence for an Aneugenic Mechanism of Action for Micronucleus Induction by Black Cohosh Extract
Evidence for an Aneugenic Mechanism of Action for Micronucleus Induction by Black Cohosh Extract Open
Black cohosh extract (BCE) is a popular botanical dietary supplement marketed to relieve symptoms of various gynecological ailments. Studies conducted by the National Toxicology Program (NTP) showed that BCE induces micronucleated erythroc…
View article: Aneugen Molecular Mechanism Assay: Proof-of-Concept With 27 Reference Chemicals
Aneugen Molecular Mechanism Assay: Proof-of-Concept With 27 Reference Chemicals Open
A tiered bioassay and data analysis scheme is described for elucidating the most common molecular targets responsible for chemical-induced in vitro aneugenicity: tubulin destabilization, tubulin stabilization, and inhibition of mitotic kin…
View article: Black cohosh extracts and powders induce micronuclei, a biomarker of genetic damage, in human cells
Black cohosh extracts and powders induce micronuclei, a biomarker of genetic damage, in human cells Open
Black cohosh extract (BCE) is a widely used dietary supplement marketed to women to alleviate symptoms of gynecological ailments, yet its toxicity has not been well characterized. The National Toxicology Program (NTP) previously reported s…
View article: Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells
Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells Open
TEMPO (2, 2, 6, 6-tetramethylphiperidine-1-oxyl) and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei …
View article: Investigating the Generalizability of the MultiFlow ® DNA Damage Assay and Several Companion Machine Learning Models With a Set of 103 Diverse Test Chemicals
Investigating the Generalizability of the MultiFlow ® DNA Damage Assay and Several Companion Machine Learning Models With a Set of 103 Diverse Test Chemicals Open
The in vitro MultiFlow DNA Damage assay multiplexes p53, γH2AX, phospho-histone H3, and polyploidization biomarkers into 1 flow cytometric analysis (Bryce, S. M., Bernacki, D. T., Bemis, J. C., and Dertinger, S. D. (2016). Genotoxic mode o…
View article: Interlaboratory evaluation of a multiplexed high information content in vitro genotoxicity assay
Interlaboratory evaluation of a multiplexed high information content in vitro genotoxicity assay Open
We previously described a multiplexed in vitro genotoxicity assay based on flow cytometric analysis of detergent‐liberated nuclei that are simultaneously stained with propidium iodide and labeled with fluorescent antibodies against p53, γH…
View article: Genotoxic mode of action predictions from a multiplexed flow cytometric assay and a machine learning approach
Genotoxic mode of action predictions from a multiplexed flow cytometric assay and a machine learning approach Open
Several endpoints associated with cellular responses to DNA damage as well as overt cytotoxicity were multiplexed into a miniaturized, “add and read” type flow cytometric assay. Reagents included a detergent to liberate nuclei, RNase and p…
View article: Comparison of<i>in vitro</i>and<i>in vivo</i>clastogenic potency based on benchmark dose analysis of flow cytometric micronucleus data
Comparison of<i>in vitro</i>and<i>in vivo</i>clastogenic potency based on benchmark dose analysis of flow cytometric micronucleus data Open
The application of flow cytometry as a scoring platform for both in vivo and in vitro micronucleus (MN) studies has enabled the efficient generation of high quality datasets suitable for comprehensive assessment of dose-response. Using thi…