ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Pig-a mutation: kinetics in rat erythrocytes following exposure to five prototypical mutagens.
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 19 papers.
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Who cites it
19 citing papers in PubMed, 92 citations in OpenAlex.
- N-Nitrosodimethylamine investigations in Muta™Mouse define point-of-departure values and demonstrate less-than-additive somatic mutant frequency accumulations.Mutagenesis · 2024Article
- Recommendations for conducting the rodent erythrocyte Pig-a assay: A report from the HESI GTTC Pig-a Workgroup.Environmental and molecular mutagenesis · 2021Review
- Pig-a gene mutation assay study design: critical assessment of 3- versus 28-day repeat-dose treatment schedules.Mutagenesis · 2020Article
- Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays.Mutagenesis · 2020Article
- 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
- Integrated In Vivo Genotoxicity Assessment of Procarbazine Hydrochloride Demonstrates Induction of Pig-a and LacZ Mutations, and Micronuclei, in MutaMouse Hematopoietic Cells.Environmental and molecular mutagenesis · 2019Article
- In vivo pig-a and micronucleus study of the prototypical aneugen vinblastine sulfate.Environmental 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
- Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane.Mutagenesis · 2015Article
- 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
- 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
- Persistence of cisplatin-induced mutagenicity in hematopoietic stem cells: implications for secondary cancer risk following chemotherapy.Toxicological sciences : an official journal of the Society of Toxicology · 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
- Integration of mutation and chromosomal damage endpoints into 28-day repeat dose toxicology studies.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
An in vivo mutation assay has been developed based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient rat erythrocytes. With this method, blood is incubated with anti-CD59-PE and SYTO 13 dye, and flow cytometry is used to score the frequency of CD59-negative erythrocytes. The experiments described herein were designed to define the kinetics of mutant erythrocyte appearance and disappearance from peripheral blood to support appropriate treatment and sampling designs for the assay. Wistar Han rats were treated with one of five prototypical mutagens: N-ethyl-N-nitrosourea (ENU); 7,12-dimethyl-1,2-benz[a]anthracene (DMBA); 4-nitroquinoline-1-oxide; benzo[a]pyrene; and N-methyl-N-nitrosourea. ENU and DMBA were also evaluated in Sprague Dawley rats. Animals were treated on three consecutive days (days 1-3) via oral gavage, and blood specimens were obtained on days -1, 4, 15, 30, 45, and 90 (and day 180 for ENU). A second endpoint of genotoxicity, the frequency of peripheral blood micronucleated reticulocytes, was measured on day 4. Each chemical induced micronuclei and the GPI anchor-deficient phenotype. Increased mutant cell frequencies were evident at day 15. Mutant reticulocyte frequencies remained relatively stable for some chemicals, but others peaked and then dropped significantly. The differences in kinetics observed are presumably related to the degree to which mutation occurs in hematopoietic stem cells versus more committed cells with limited self-renewal capacity. Collectively, the results suggest that enumerating GPI anchor-deficient erythrocytes is an efficient means of evaluating the in vivo mutagenic potential of chemicals. The kinetics and ease of scoring this blood-based endpoint suggest that integration into routine toxicology studies will be feasible.
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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.