Abstract:
:A collaborative international trial was conducted to evaluate the reproducibility and transferability of an in vivo mutation assay based on the enumeration of CD59-negative rat erythrocytes, a phenotype that is indicative of Pig-a gene mutation. Fourteen laboratories participated in this study, where anti-CD59-PE, SYTO 13 dye, and flow cytometry were used to determine the frequency of CD59-negative erythrocytes (RBC(CD59-)) and CD59-negative reticulocytes (RET(CD59-)). To provide samples with a range of mutant phenotype cell frequencies, male rats were exposed to N-ethyl-N-nitrosourea (ENU) via oral gavage for three consecutive days (Days 1-3). Each laboratory studied 0, 20, and 40 mg ENU/kg/day (n = 5 per group). Three sites also evaluated 4 mg/kg/day. At a minimum, blood samples were collected three times: predosing and on Days 15 and 30. Blood samples were processed according to a standardized sample processing and data acquisition protocol, and three endpoints were measured: %reticulocytes, frequency of RET(CD59-) , and frequency of RBC(CD59-) . The methodology was found to be reproducible, as the analysis of technical replicates resulted in experimental coefficients of variation that approached theoretical values. Good transferability was evident from the similar kinetics and magnitude of the dose-related responses that were observed among different laboratories. Concordance correlation coefficients showed a high level of agreement between the reference site and the test sites (range: 0.87-0.99). Collectively, these data demonstrate that with adequate training of personnel, flow cytometric analysis is capable of reliably enumerating mutant phenotype erythrocytes, thereby providing a robust in vivo mutation assay that is readily transferable across laboratories.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Dertinger SD,Phonethepswath S,Weller P,Nicolette J,Murray J,Sonders P,Vohr HW,Shi J,Krsmanovic L,Gleason C,Custer L,Henwood A,Sweder K,Stankowski LF Jr,Roberts DJ,Giddings A,Kenny J,Lynch AM,Defrain C,Nesslany F,vdoi
10.1002/em.20672subject
Has Abstractpub_date
2011-12-01 00:00:00pages
690-8issue
9eissn
0893-6692issn
1098-2280journal_volume
52pub_type
杂志文章abstract::The cytotoxicity and mutagenicity of the human carcinogen, treosulphan, and its hydrolysis product, dl-1,2:3,4-diepoxybutane (DEB), were studied in Chinese hamster ovary, AS52, cells. Treosulphan (0.1-1.0 mM) is toxic and mutagenic at the gpt locus. A strong pH dependence was noted. DEB is cytotoxic and mutagenic at a...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850210113
更新日期:1993-01-01 00:00:00
abstract::Iron oxide nanoparticles (ION) are gaining importance as diagnostic and therapeutic tool of central nervous system diseases. Although oleic acid-coated ION (O-ION) have been described as stable and biocompatible, their potential neurotoxicity was scarcely evaluated in human nervous cells so far. The primary aim of thi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22323
更新日期:2019-12-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850170204
更新日期:1991-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20275
更新日期:2007-01-01 00:00:00
abstract::The genotoxicity of humic acid and its possible interaction with the herbicides alachlor and maleic hydrazide have been evaluated in cultured human lymphocytes from two donors. Humic acid and the two herbicides have been tested (alone and combined) for sister-chromatid exchange (SCE) induction. In addition, the effect...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1997)29:3<272::aid-em7>3.0
更新日期:1997-01-01 00:00:00
abstract::The importance of inherited mutations as a cause of human disease has been established clearly through examples of well-defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subs...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850110311
更新日期:1988-01-01 00:00:00
abstract::Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system containing glutathione (GSH), purified gamma-glutamyl transpeptidase (GGT), and EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration,...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1997)29:1<73::aid-em10>3.0
更新日期:1997-01-01 00:00:00
abstract::Experiments are described which elucidate some of the technical problems associated with the direct sequencing of polymerase chain reaction (PCR) amplified DNA. Sequencing primer purity, labeling methodology, and template preparation were explored. Conditions are presented for the routine sequencing of single- and dou...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850180413
更新日期:1991-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22113
更新日期:2018-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)28:2<100::AID-EM5>3.0
更新日期:1996-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10099
更新日期:2002-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1998)32:3<251::aid-em8>3.0
更新日期:1998-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850210114
更新日期:1993-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20604
更新日期:2011-03-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850210402
更新日期:1993-01-01 00:00:00
abstract::A recent study conducted by our group showed that the NAT2 fast acetylator genotype is associated with an increasing risk for the development of colorectal cancer (CRC), especially for females. We therefore examined whether a higher risk of CRC in females with the NAT2 fast acetylator genotype was associated with the ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20444
更新日期:2009-03-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20328
更新日期:2007-10-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)27:1<67::AID-EM9>3.0.
更新日期:1996-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22154
更新日期:2018-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850240305
更新日期:1994-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850200409
更新日期:1992-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20457
更新日期:2009-05-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22240
更新日期:2018-12-01 00:00:00
abstract::Early results from two transgenic mouse mutation assays, Big Blue [Kohler SW et al. (1991): Proc Natl Acad Sci USA 88:7958-7962] and Muta Mouse [Myhr BC (1991): Environ Mol Mutagen 18:308-315], raised questions about appropriate study design and methods for statistical analysis. First, there were a number of potential...
journal_title:Environmental and molecular mutagenesis
pub_type:
doi:10.1002/em.2850230104
更新日期:1994-01-01 00:00:00
abstract::Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21786
更新日期:2013-07-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.22319
更新日期:2019-10-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850190105
更新日期:1992-01-01 00:00:00
abstract::The mitochondrial genome is essential for producing ATP (adenosine 5'-triphosphate) via oxidative phosphorylation. The gradual decline of mitochondrial function with age has long been postulated as a factor in aging. More recently, a variety of diseases have been related to molecular defects in human mitochondrial DNA...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850250607
更新日期:1995-01-01 00:00:00
abstract::We describe an in vivo mutagenesis model that utilizes reverse mutation and forward mutation at the endogenous Aprt locus. Reverse mutation provides an in situ method for detecting environments or agents that cause point mutations. Forward mutation detects large chromosomal events, including mitotic recombination, chr...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)28:4<471::AID-EM25>3.
更新日期:1996-01-01 00:00:00