Evaluation of Macaca mulatta as a model for genotoxicity studies

Dobrovolsky, Vasily N.; Shaddock, Joseph G.; Mittelstaedt, Roberta A.; Manjanatha, Mugimane G.; Miura, Daisuke; Uchikawa, Makoto; Mattison, Donald R.; Morris, Suzanne M.

doi:10.1016/j.mrgentox.2008.11.006

Cited by 30 publications

(21 citation statements)

References 35 publications

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“…Pig-A gene mutation assay with mice peripheral blood: Recent works provided that the erythrocytebased Pig-A gene mutation assay is applicable across species (5)(6)(7)(8). According to these reports, we modiˆed the original Pig-A gene mutation assay and performed it with mice peripheral blood.…”

Section: Resultsmentioning

confidence: 99%

“…The Pig-A assay, a powerful tool for the evaluation of in vivo genotoxicity, is based on ‰ow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor-deˆcient erythrocytes and has been shown to be applicable across species from rodent to monkey (5)(6)(7)(8). With this method, we need no transgenic animals to test in vivo genotoxicity, but need only 1-2 mL peripheral blood (5,6).…”

Section: Introductionmentioning

confidence: 99%

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Fullerene (C60) Is Negative in the In Vivo Pig-A Gene Mutation Assay

Horibata

Ukai

Naoki

et al. 2011

Genes and Environment

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Carbon nanoparticles, such as carbon nanotubes and fullerene (C 60 ), are potential candidates as leading substances in nanotechnologicalˆelds, but little is known about their safety. Here we examined in vivo genotoxicity of C 60 , by performing the Pig-A gene mutation assay in the peripheral blood of male C57BL/6Cr mice. Mice were given single intraperitoneal injection of 3 mg of C 60 particles in 0.5 mL suspension containing 0.1%-Tween80-saline. As a positive control for the Pig-A gene mutation assay, mice were given a single oral administration of N-nitroso-Nethylurea. At 2 and 8 weeks after treatments, we analyzed CD24-negative and -positive red blood cells in peripheral blood and calculated Pig-A mutant frequencies. As a result, we detected no signiˆcant diŠerences in the mutant frequencies between C 60 treated and non-treated mice, indicating that C 60 is negative for genotoxicity in vivo in the limited target tissues assessed in this study. For the full assessment, we need comprehensive whole body survey on the genotoxicity of C 60 .

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fullerene (C60) Is Negative in the In Vivo Pig-A Gene Mutation Assay

Horibata

Ukai

Naoki

et al. 2011

Genes and Environment

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“…For instance, light scattering can be used to distinguish cells from platelets and an antibody specific for WBCs used to enrich the cell population for RBCs [Miura et al, 2008a], or a nucleic acid stain can be used to distinguish reticulocytes (RETs) from normochromatic erythrocytes (NCEs) ]. An additional step performed before flow cytometry may be used to enrich for the target cell population, such as gradient centrifugation of whole blood for separating RBCs from WBCs and platelets [Phonethepswath et al, 2008;Dobrovolsky et al, 2009a].…”

Section: Measurement Of Pig-a Mutant Frequenciesmentioning

confidence: 99%

“…Clonal Pig-a mutation analyses have been described for rat and rhesus monkey T-lymphocytes [Miura et al, 2008b;Dobrovolsky et al, 2009a], and preEnvironmental and Molecular Mutagenesis. DOI 10.1002/em Fig.…”

Section: Measurement Of Pig-a Mutant Frequenciesmentioning

confidence: 99%

“…A relatively high dose of ENU (100 mg/kg) induced similar RBC and Tcell Pig-a mutant frequencies, as determined by flow cytometric assays, and similar T-cell Pig-a and Hprt mutant frequencies, as determined by limiting-dilution cloning [Miura et al, 2008c]. Another study conducted on a small number of rhesus monkeys compared ENU-induced RBC Pig-a, T-cell Pig-a, and T-cell Hprt mutant frequencies [Dobrovolsky et al, 2009a]. Again, all the ENUinduced mutant frequencies were comparable.…”

Section: Observations On the Sensitivity Of The Rat Pig-a Assaymentioning

confidence: 99%

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The in vivo pig‐a gene mutation assay, a potential tool for regulatory safety assessment

Dobrovolsky

Miura

Heflich

et al. 2010

Environ and Mol Mutagen

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116

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The Pig-a (phosphatidylinositol glycan, Class A) gene codes for a catalytic subunit of the N-acetylglucosamine transferase complex involved in an early step of glycosylphosphatidyl inositol (GPI) cell surface anchor synthesis. Pig-a is the only gene involved in GPI anchor synthesis that is on the X-chromosome, and research into the origins of an acquired genetic disease involving GPI anchor deficiency (paroxysmal nocturnal hemoglobinuria) indicates that cells lacking GPI anchors, or GPI-anchored cell surface proteins, almost always have mutations in the Pig-a gene. These properties of the Pig-a gene and the GPI anchor system have been exploited in a series of assays for measuring in vivo gene mutation in blood cells from humans, rats, mice, and monkeys. In rats, flow cytometric measurement of Pig-a mutation in red blood cells requires microliter volumes of blood and data can be generated in hours. Spontaneous mutant frequencies are relatively low (<5 × 10(-6)) and rats treated with multiple doses of the potent mutagen, N-ethyl-N-nitrosourea, display Pig-a mutant frequencies that are close to the sum of the frequencies produced by the individual exposures. A general observation is that induced mutant frequencies are manifested earlier in reticulocytes (about 2 weeks after treatment) than in total red blood cells (about 2 months after exposure). Based on data from a limited number of test agents, the assay shows promise for regulatory applications, including integration of gene mutation measurement into repeat-dose toxicology studies.

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The Role of Nonhuman Primates in Neurotoxicology Research: Preclinical Models and Experimental Methods

2023

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Although noteworthy progress has been made in developing alternatives to animal testing, nonhuman primates still play a critical role in advancing biomedical research and will likely do so for many years. Core similarities between monkeys and humans in genetics, physiology, reproduction, development, and behavior make them excellent models for translational studies relevant to human health. This unit is designed to specifically address the role of nonhuman primates in neurotoxicology research and outlines the specialized assessments that can be used to measure exposure-related changes at the structural, chemical, cellular, molecular, and functional levels.

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Evaluation of Macaca mulatta as a model for genotoxicity studies

Cited by 30 publications

References 35 publications

Fullerene (C60) Is Negative in the In Vivo Pig-A Gene Mutation Assay

Fullerene (C60) Is Negative in the In Vivo Pig-A Gene Mutation Assay

The in vivo pig‐a gene mutation assay, a potential tool for regulatory safety assessment

The Role of Nonhuman Primates in Neurotoxicology Research: Preclinical Models and Experimental Methods

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