ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Integration of mutation and chromosomal damage endpoints into 28-day repeat dose toxicology studies.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 91 citations in OpenAlex.
- Erythrocyte-Based Pig-a Gene Mutation Assay.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Genotoxicity assessment: opportunities, challenges and perspectives for quantitative evaluations of dose-response data.Archives of toxicology · 2023Review
- 3Rs friendly study designs facilitate rat liver and blood micronucleus assays and Pig-a gene mutation assessments: Proof-of-concept with 13 reference chemicals.Environmental and molecular mutagenesis · 2019Article
- Integration of liver and blood micronucleus and Pig-a gene mutation endpoints into rat 28-day repeat-treatment studies: Proof-of-principle with diethylnitrosamine.Mutation research. Genetic toxicology and environmental mutagenesis · 2018Article
- Glycosylphosphatidylinositol (GPI) anchored protein deficiency serves as a reliable reporter of Pig-a gene Mutation: Support from an in vitro assay based on L5178Y/TkEnvironmental and molecular mutagenesis · 2018Article
- Comparison of integrated genotoxicity endpoints in rats after acute and subchronic oral doses of 4-nitroquinoline-1-oxide.Environmental and molecular mutagenesis · 2016Article
- Rat Pig-a mutation assay responds to the genotoxic carcinogen ethyl carbamate but not the non-genotoxic carcinogen methyl carbamate.Mutagenesis · 2015Article
- Human erythrocyte PIG-A assay: an easily monitored index of gene mutation requiring low volume blood samples.Environmental and molecular mutagenesis · 2015Article
- Comparison of male versus female responses in the Pig-a mutation assay.Mutagenesis · 2015Article
- Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane.Mutagenesis · 2015Article
- Induction of Pig-a mutant erythrocytes in male and female rats exposed to 1,3-propane sultone, ethyl carbamate, or thiotepa.Mutation research. Genetic toxicology and environmental mutagenesis · 2015Article
- Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing.Journal of the American Association for Laboratory Animal Science : JAALAS · 2015Article
- Single cell gel electrophoresis (SCGE) and Pig-a mutation assay in vivo-tools for genotoxicity testing from a regulatory perspective: a study of benzo[a]pyrene in Ogg1(-/-) mice.Mutation research. Genetic toxicology and environmental mutagenesis · 2014Article
- Efficient monitoring of in vivo pig-a gene mutation and chromosomal damage: summary of 7 published studies and results from 11 new reference compounds.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Simultaneous measurement of benzo[a]pyrene-induced Pig-a and lacZ mutations, micronuclei and DNA adducts in Muta™ Mouse.Environmental and molecular mutagenesis · 2011Article
- Defining EMS and ENU dose-response relationships using the Pig-a mutation assay in rats.Mutation research · 2011Article
- When pigs fly: immunomagnetic separation facilitates rapid determination of Pig-a mutant frequency by flow cytometric analysis.Mutation research · 2011Article
- How accurate is in vitro prediction of carcinogenicity?British journal of pharmacology · 2011Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Two endpoints of genetic toxicity, mutation at the X-linked Pig-a gene and chromosomal damage in the form of micronucleated reticulocytes (MN-RETs), were evaluated in blood samples obtained from 28-day repeat-dosing studies typical of those employed in toxicity evaluations. Male Wistar Han rats were treated at 24-h intervals on days 1 through 28 with one of five prototypical genotoxicants: N-ethyl-N-nitrosourea, 7,12-dimethyl-12-benz[a]anthracene, 4-nitroquinoline-1-oxide (4NQO), benzo(a)pyrene, and N-methyl-N-nitrosourea. Flow cytometric scoring of CD59-negative erythrocytes (indicative of glycosylphosphatidylinositol anchor deficiency and hence Pig-a mutation) was performed using blood specimens obtained on days -1, 15, 29, and 56. Blood specimens collected on days 4 and 29 were evaluated for MN-RET frequency using flow cytometry-based MicroFlow Kits. With the exception of 4NQO, each chemical induced significant increases in the frequency of MN-RETs on days 4 and 29. All five agents increased the frequency of mutant phenotype (CD59 negative) reticulocytes (RETs) and erythrocytes. Mutation responses in RETs occurred earlier than in erythrocytes and tended to peak, or nearly peak, at day 29. In contrast, the mutant phenotype erythrocyte responses were modest on day 29 and required additional time to reach their maximal value. The observed kinetics were expected based on the known turnover of RETs and erythrocytes. The data show that RETs can serve as an appropriate indicator cell population for 28-day studies. Collectively, these data suggest that blood-based genotoxicity endpoints can be effectively incorporated into routine toxicology studies, a strategy that would reduce animal usage while providing valuable genetic toxicity information within the context of other toxicological endpoints.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.