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

2010 ◽  
Vol 51 (8-9) ◽  
pp. 825-835 ◽  
Author(s):  
Vasily N. Dobrovolsky ◽  
Daishiro Miura ◽  
Robert H. Heflich ◽  
Stephen D. Dertinger
Keyword(s):  
Gene Mutation ◽  
Safety Assessment ◽  
Mutation Assay ◽  
Gene Mutation Assay ◽  
Potential Tool

scholarly journals The in vivo Pig-a gene mutation assay is applied to study the genotoxicity of procarbazine hydrochloride in Sprague-Dawley rats

2016 ◽  
Vol 3 (4) ◽  
pp. 167-175 ◽  
Author(s):  
Jiang Pu ◽  
Yuanyuan Deng ◽  
Xiaoyan Tan ◽  
Gaofeng Chen ◽  
Cong Zhu ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Mutation Assay ◽  
Gene Mutation Assay

Application of the in vivo Pig-a gene mutation assay to test the potential genotoxicity of p-phenylenediamine

2019 ◽  
Vol 123 ◽  
pp. 424-430 ◽  
Author(s):  
Meirong Qin ◽  
Runhua Chen ◽  
Zeyu Huang ◽  
Jinping Wang ◽  
Suowen Xu ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Mutation Assay ◽  
Gene Mutation Assay

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

2011 ◽  
Vol 33 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Katsuyoshi Horibata ◽  
Akiko Ukai ◽  
Naoki Koyama ◽  
Atsuya Takagi ◽  
Jun Kanno ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Fullerene C60 ◽  
Mutation Assay ◽  
Gene Mutation Assay

Development of an in vivo gene mutation assay using the endogenousPig-Agene: II. Selection ofPig-Amutant rat spleen T-cells with proaerolysin and sequencingPig-AcDNA from the mutants

2008 ◽  
Vol 49 (8) ◽  
pp. 622-630 ◽  
Author(s):  
Daishiro Miura ◽  
Vasily N. Dobrovolsky ◽  
Roberta A. Mittelstaedt ◽  
Yoshinori Kasahara ◽  
Yasuhiro Katsuura ◽  
...  
Keyword(s):  
T Cells ◽  
Gene Mutation ◽  
Mutation Assay ◽  
Gene Mutation Assay

Studies of the Toxicological Potential of Capsinoids: V. Genotoxicity Studies of Dihydrocapsiate

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 59-72 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Chromosomal Aberration ◽  
Metabolic Activation ◽  
Transgenic Rats ◽  
Negative Results ◽  
Chromosomal Aberration Test ◽  
Mutation Assay ◽  
Gene Mutation Assay

A series of studies was performed to evaluate the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS no. 205687-03-2). This study evaluated the potential genotoxicity of this compound using a variety of in vitro and in vivo test systems, including bacterial reverse mutation test, chromosomal aberration test, micronucleus test, gene mutation assay with transgenic rats, and single-cell gel (SCG) assay (Comet assay). In vitro tests (bacterial reverse mutation test and chromosomal aberration test) produced positive results in the absence of metabolic activation, but negative results in the presence of metabolic activation. The in vivo gene mutation assay (with transgenic rats) produced negative results, as did the in vivo mouse micronucleus assay, which failed to induce micronucleated polychromatic erythrocytes. Although the rat SCG assay produced statistically significant increases in the Olive tail moment and % tail DNA of the liver and intestine in the 2000 mg/kg group (compared with the negative-control group), a number of factors caused the authors to question the validity of these findings. Taken together, these results suggest that dihydrocapsiate has a low or extremely low likelihood of inducing genotoxicity.

Toxicology of Diethylene Glycol Butyl Ether 3. Genotoxicity Evaluation in an In Vitro Gene Mutation Assay and an In Vivo Cytogenetic Test

1993 ◽  
Vol 12 (2) ◽  
pp. 155-159 ◽  
Author(s):  
B. Bhaskar Gollapudi ◽  
V. A. Linscombe ◽  
M. L. Mcclintock ◽  
A. K. Sinha ◽  
C. R. Stack
Keyword(s):  
Bone Marrow ◽  
Gene Mutation ◽  
Micronucleus Test ◽  
Mouse Bone Marrow ◽  
Butyl Ether ◽  
Polychromatic Erythrocytes ◽  
Mutation Assay ◽  
Gene Mutation Assay

DGBE was evaluated in a forward gene mutation assay at the HGPRT locus of CHO cells in culture and in an in vivo mouse bone marrow micronucleus test for cytogenetic damage. DGBE did not elicit a positive response in the CHO/HGPRT assay when tested up to a maximum concentration of 5000 μg/ml with and without an external metabolic activation system (S-9). In the micronucleus test employing three post-treatment bone marrow sampling times (24, 48, and 72 hr), DGBE was ineffective in increasing the incidence of micronucleated polychromatic erythrocytes (MN-PCE) when tested in both sexes up to a maximum tolerated dose of 3300 mg/kg body weight. Thus, these data and those of others indicate a general lack of genotoxic potential for DGBE in short-term tests.

scholarly journals In Vitro PIG-A Gene Mutation Assay in Human B-Lymphoblastoid TK6 Cells

2021 ◽  
Vol 03 (02) ◽  
pp. e77-e85
Author(s):  
Chang-Hui Zhou ◽  
Chun-Rong Yu ◽  
Peng-Cheng Huang ◽  
Ruo-Wan Li ◽  
Jing-Ting Wang ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Mutation Frequency ◽  
Negative Control ◽  
Protein Markers ◽  
Tk6 Cells ◽  
Mutation Assay ◽  
Mutant Cells ◽  
Gene Mutation Assay

AbstractThe X-linked PIG-A gene is involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. PIG-A mutant cells fail to synthesize GPI and to express GPI-anchored protein markers (e.g., CD59 and CD55). In recent years, in vitro PIG-A assay has been established based on the high conservation of PIG-A/Pig-a loci among different species and the large data from the in vivo system. The purpose of this study was to extend the approach for PIG-A mutation assessment to in vitro human B-lymphoblastoid TK6 cells by detecting the loss of GPI-linked CD55 and CD59 proteins. TK6 cells were treated with three mutagens 7,12-dimethylbenz[a]anthracene (DMBA), N-ethyl-N-nitrosourea (ENU), etoposide (ETO), and two nonmutagens: cadmium chloride (CdCl2) and sodium chloride (NaCl). The mutation rate of PIG-A gene within TK6 cells was determined on the 11th day with flow cytometry analysis for the negative frequencies of CD55 and CD59. The antibodies used in this production were APC mouse-anti-human CD19 antibody, PE mouse anti-human CD55 antibody, PE mouse anti-human CD59 antibody, and nucleic acid dye 7-AAD. An immunolabeling method was used to reduce the high spontaneous level of preexisting PIG-A mutant cells. Our data suggested that DMBA-, ENU-, and ETO-induced mutation frequency of PIG-A gene was increased by twofold compared with the negative control, and the effects were dose-dependent. However, CdCl2 and NaCl did not significantly increase the mutation frequency of PIG-A gene, with a high cytotoxicity at a dose of 10 mmol/L. Our study suggested that the novel in vitro PIG-A gene mutation assay within TK6 cells may represent a complement of the present in vivo Pig-a assay, and may provide guidance for their potential use in genotoxicity even in cells with a significant deficiency of GPI anchor.

scholarly journals The In Vivo Pig-a Gene Mutation Assay

2014 ◽  
Vol 36 (4) ◽  
pp. 169-173 ◽  
Author(s):  
Daishiro Miura
Keyword(s):  
Gene Mutation ◽  
Mutation Assay ◽  
Gene Mutation Assay

A statistical approach for analyzing data from the in vivo Pig-a gene mutation assay

2018 ◽  
Vol 831 ◽  
pp. 33-44
Author(s):  
Bernd-Wolfgang Igl ◽  
Stephen D. Dertinger ◽  
Vasily N. Dobrovolsky ◽  
Marian Raschke ◽  
Andreas Sutter ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Statistical Approach ◽  
Mutation Assay ◽  
Gene Mutation Assay
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