The<i>Salmonella</i>Mutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21st Century

Claxton, Larry D.; Umbuzeiro, Gisela de Aragão; DeMarini, David M.

doi:10.1289/ehp.1002336

Cited by 133 publications

(99 citation statements)

References 155 publications

(200 reference statements)

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“…This was originally considered suitable because mutagenic potential was thought to be a rare property of only a few chemicals to which exposure could simply be prevented. However, with accumulating experience, it has become apparent that many chemicals, both synthetic and natural, can induce genetic damage [Galloway et al, 1987;Moore and Brock, 1988;Seeberg et al, 1988;Kultz and Chakravarty, 2001;Charles et al, 2002;Claxton et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Gollapudi

Johnson

Hernández

et al. 2012

Environ and Mol Mutagen

132

130

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Genetic toxicology studies are required for the safety assessment of chemicals. Data from these studies have historically been interpreted in a qualitative, dichotomous ''yes'' or ''no'' manner without analysis of doseresponse relationships. This article is based upon the work of an international multi-sector group that examined how quantitative dose-response relationships for in vitro and in vivo genetic toxicology data might be used to improve human risk assessment. The group examined three quantitative approaches for analyzing dose-response curves and deriving point-of-departure (POD) metrics (i.e., the no-observed-genotoxic-effectlevel (NOGEL), the threshold effect level (Td), and the benchmark dose (BMD)), using data for the induction of micronuclei and gene mutations by methyl methanesulfonate or ethyl methanesulfonate in vitro and in vivo. These results suggest that the POD descriptors obtained using the different approaches are within the same order of magnitude, with more variability observed for the in vivo assays. The different approaches were found to be complementary as each has advantages and limitations. The results further indicate that the lower confidence limit of a benchmark response rate of 10% (BMDL 10 ) could be considered a satisfactory POD when analyzing genotoxicity data using the BMD approach. The models described permit the identification of POD values that could be combined with mode of action analysis to determine whether exposure(s) below a particular level constitutes a significant human risk. Subsequent analyses will expand the number of substances and endpoints investigated, and continue to evaluate the utility of quantitative approaches for analysis of genetic toxicity dose-response data. Environ. Mol. Mutagen. 54:8-18, 2013. V V C 2012 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Gollapudi

Johnson

Hernández

et al. 2012

Environ and Mol Mutagen

132

130

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“…As my colleagues and I have noted and reviewed [Claxton et al, 2010], there was almost no knowledge of the prevalence of somatic-cell mutagens in our environment prior to the introduction by B.N. Ames of the Salmonella mutagenicity assay in 1971.…”

Section: Need For a Declaration Panel And Implications Of Declaring Amentioning

confidence: 99%

“…However, by 1978, the first studies were reported using this assay showing that chlorinated water, urban air, and grilled fish were mutagenic; even something as noxious as cigarette smoke went unrecognized as a mutagen until it was tested in the Salmonella mutagenicity assay in 1974. Furthermore, a series of key experiments in this assay culminated in 1973 in the first clear linkage between mutagenesis and carcinogenesis [Claxton et al, 2010]. Thus, the paradigm shifts linking mutagenicity with carcinogenicity, as well as showing the ubiquitous presence of environmental mutagens, did not occur until the application of a new technology, the Salmonella mutagenicity assay [Claxton et al, 2010].…”

Section: Need For a Declaration Panel And Implications Of Declaring Amentioning

confidence: 99%

“…Furthermore, a series of key experiments in this assay culminated in 1973 in the first clear linkage between mutagenesis and carcinogenesis [Claxton et al, 2010]. Thus, the paradigm shifts linking mutagenicity with carcinogenicity, as well as showing the ubiquitous presence of environmental mutagens, did not occur until the application of a new technology, the Salmonella mutagenicity assay [Claxton et al, 2010].…”

Section: Need For a Declaration Panel And Implications Of Declaring Amentioning

confidence: 99%

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Declaring the existence of human germ‐cell mutagens

DeMarini

2012

Environ and Mol Mutagen

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After more than 80 years of searching for human germ‐cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application of recently developed genomic techniques. In preparation for this, an assessment panel of internationally recognized experts in germ‐cell biology and genomics is required to consider either the current evidence now, or impending genomic evidence later, to declare whether an agent is a human germ‐cell mutagen. I propose that such a panel be organized under the aegis of the World Health Organization and constructed similarly to the working groups assembled by the International Agency for Research on Cancer for the evaluation of human carcinogens. Support from prominent national and international organizations would be important. Many regulatory agencies already have procedures in place for assessing potential human germ‐cell mutagens, and the time is approaching when definitive genomic data in humans will obligate such evaluations. In my view, application of an IARC‐type of assessment using available evidence leads to the conclusion that ionizing radiation, cancer chemotherapy, cigarette smoking, and air pollution are “Group 1” human germ‐cell mutagens. Consideration of the potential adverse health effects to the unexposed offspring of an exposed parent will usher in an entirely new realm of environmental health assessment. I suggest that the long search for human germ‐cell mutagens is about to end, and a demonstration of the much‐anticipated linkage between heritable disease and environmental factors is poised to begin. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.

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“…This test serves as a model for predicting and understanding the toxicological properties of the test substance (Claxton et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Antigenotoxic, and anticytotoxic activities of an ethanolic extract of Lafoensia pacari (Lythraceae) stem bark in bacteria and mice

Fd¹,

Silva²,

Sampaio³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Lafoensia pacari (Lythraceae), popularly known in Brazil as "pacari", is a small tree native to the Cerrado that is used in folk medicine to treat cancer and as an anti-inflammatory and cicatrizing agent. We evaluated the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of an ethanol extract of L. pacari stem bark (EESB) using the Ames test and the mouse bone marrow micronucleus test. In the Ames test, EESB did not significantly increase the number of His + revertants in Salmonella typhimurium tester strains TA98 and TA100 at all doses, demonstrating lack of mutagenicity. Only the highest dose of EESB significantly increased the micronucleated polychromatic erythrocyte frequency in the micronucleus test, indicating mild genotoxicity. EESB produced a mutagenic index lower than the negative control in the Ames test. In the micronucleus test, at all doses, EESB caused a significant decrease in the polychromatic/normochromatic erythrocyte ratio (PCE/NCE) at 24 h compared with the negative control. EESB co-administered together with the respective positive control caused a significant decrease in the number of His + revertant colonies in the Ames test and in the frequency of micronucleated polychromatic erythrocytes in the micronucleus test, demonstrating a DNA protector effect. EESB co-administered with mitomycin C significantly increased the PCE/NCE ratio at all doses, showing an anticytotoxic effect. We conclude that EESB has antigenotoxic and anticytotoxic properties.

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TheSalmonellaMutagenicity Assay: The Stethoscope of Genetic Toxicology for the 21st Century

Cited by 133 publications

References 155 publications

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Quantitative approaches for assessing dose–response relationships in genetic toxicology studies

Declaring the existence of human germ‐cell mutagens

Antigenotoxic, and anticytotoxic activities of an ethanolic extract of Lafoensia pacari (Lythraceae) stem bark in bacteria and mice

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