Mutagenesis and mathematics: The allure of numbers

Haynes, Robert H.

doi:10.1002/em.2850140308

Cited by 9 publications

(2 citation statements)

References 20 publications

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“…The lacZ MF data were analyzed in using RStudio version 1.0.136 (RStudio, Boston, MA) software using the glm function. The quasi‐Poisson distribution family was used to account for overdispersion, and the offset was designated as the natural log of total pfu (Haynes, ). Type 1, or sequential analysis, was employed to examine the statistical significance of the chemical treatment (i.e., Chi‐squared test), and custom contrasts statements were employed to evaluate the statistical significance of responses at selected doses or concentrations (Arlt et al, ).…”

Section: Methodsmentioning

confidence: 99%

The development and prevalidation of anin vitromutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals

Cox

Zwart

Luijten

et al. 2019

Environ and Mol Mutagen

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As demonstrated in Part I, cultured MutaMouse primary hepatocytes (PHs) are suitable cells for use in an in vitro gene mutation assay due to their metabolic competence, their “normal” phenotype, and the presence of the MutaMouse transgene for reliable mutation scoring. The performance of these cells in an in vitro gene mutation assay is evaluated in this study, Part II. A panel of 13 mutagenic and nonmutagenic compounds was selected to investigate the performance of the MutaMouse PH in vitro gene mutation assay. The nine mutagens represent a range of classes of chemicals and include mutagens that are both direct‐acting and requiring metabolic activation. All the mutagens tested, except for ICR 191, elicited significant, concentration‐dependent increases in mutant frequency (MF) ranging from 2.6‐ to 14.4‐fold over the control. None of the four nonmutagens, including two misleading, or “false,” positives (i.e., tertiary butylhydroquinone [TBHQ] and eugenol), yielded any significant increases in MF. The benchmark dose covariate approach facilitated ranking of the positive chemicals from most (i.e., 3‐nitrobenzanthrone [3‐NBA], benzo[ a ]pyrene [BaP], and aflatoxin B 1 [AFB1]) to least (i.e., N ‐ethyl‐ N ‐nitrosourea [ENU]) potent. Overall, the results of this preliminary validation study suggest that this assay may serve as a complimentary tool alongside the standard genotoxicity test battery. This study, alongside Part I, illustrates the promise of MutaMouse PHs for use in an in vitro gene mutation assay, particularly for chemicals requiring metabolic activation. Environ. Mol. Mutagen. 60:348–360, 2019. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

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Section: Methodsmentioning

confidence: 99%

The development and prevalidation of anin vitromutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals

Cox

Zwart

Luijten

et al. 2019

Environ and Mol Mutagen

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“…The concept as used with Ames/Salmonella data dates back to Margolin et al (1981), although the use of such biologically based stochastic models in mutation research is, of course, much older; see for example, the discussion article by Haynes (1989).…”

Section: Potency Estimation With Ames/salmonella Datamentioning

confidence: 99%

Combining environmental information via hierarchical modeling: an example using mutagenic potencies

Simmons¹,

Piegorsch²,

Nitcheva³

et al. 2003

Environmetrics

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SUMMARYMutagenesis assays of toxic environmental agents often provide only a single snapshot of the agent's potential risk, leading to inferences on a possibly isolated phenomenon. Hierarchical models can enhance inferences on environmental agents and obtain more global perspectives on the potential risk. We investigate the use of such models to combine information across environmental studies. We emphasize combination of potency estimates from bioassays used for environmental hazard identification and risk assessment. The models and methods illustrate hierarchical Bayesian techniques to estimate the parameters and make inferences on the unknown potency values.

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Mutagenicity Study

Piegorsch

2005

Encyclopedia of Biostatistics

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Biometric methods are discussed for analyzing data from bioassays of mutagenic response. Emphasis is placed on the classic microbial system in environmental mutagenesis: the Ames/ Salmonella microsome assay. The assay produces count data to quantify the mutational response; statistical issues of interest when analyzing such data include testing for extra‐Poisson variability, trend testing for a dose response, and trend testing under a nonmonotone dose response.

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Mutagenesis and mathematics: The allure of numbers

Cited by 9 publications

References 20 publications

The development and prevalidation of anin vitromutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals

The development and prevalidation of anin vitromutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals

Combining environmental information via hierarchical modeling: an example using mutagenic potencies

Mutagenicity Study

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