2011
DOI: 10.1002/em.20692
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Abstract: As part of the Stage III Pig-a multilaboratory validation trial, we examined the induction of CD59-negative reticulocytes and total red blood cells (RET(CD59-) and RBC(CD59-) , respectively) in male Sprague Dawley(®) rats treated with 4-nitroquinoline-1-oxide (4NQO), for 28 consecutive days by oral gavage, at doses of 1.25, 2.50, 3.75, 5.00, and 7.50 mg kg(-1) day(-1) (the high dose group was sacrificed on Day 15 due to excessive morbidity/mortality). Animals also were evaluated for: micronucleated reticulocyt… Show more

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Cited by 40 publications
(45 citation statements)
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“…4-NQO forms stable quinoline monoadducts with purine bases through the enzymatic reduction of its nitro group (Kondo, 1977). A previous report described timeand dose-dependent increases of Pig-a mutant RBCs in rats treated with 4-NQO (Stankowski et al, 2011). In the present study, we demonstrated that both the CD45/CD59 and HIS49/CD59 assay detected similar Pig-a mutant responses.…”
Section: Discussionsupporting
confidence: 69%
“…4-NQO forms stable quinoline monoadducts with purine bases through the enzymatic reduction of its nitro group (Kondo, 1977). A previous report described timeand dose-dependent increases of Pig-a mutant RBCs in rats treated with 4-NQO (Stankowski et al, 2011). In the present study, we demonstrated that both the CD45/CD59 and HIS49/CD59 assay detected similar Pig-a mutant responses.…”
Section: Discussionsupporting
confidence: 69%
“…Within the group of agents that have been tested, the Workgroup noted two reports of assays (using 3-and 28-day treatments with aristolochic acids and 28-day treatments with 4-NQO) that were negative for erythrocyte MN induction, but positive for Pig-a mutation [27,32]. There also were 3 agents identified by the Workgroup (AZT, hydroxyurea and 5-fluorouracil) that induced micronucleated RETs but did not increase Pig-a mutant erythrocyte frequencies.…”
Section: Figmentioning
confidence: 92%
“…2 and Table 3). There is, however, good evidence for a high degree of inter-laboratory transferability and reproducibility based on the results with several potent and weak mutagens (and low doses of potent mutagens) that were tested in a systematic manner as part of the Litron trial [22][23][24][25][26][27]. This trial employed common protocols (refined for each stage of the trial), and common reagents, although the rat strains and flow cytometers used were at the discretion of the participating laboratory.…”
Section: Intra/inter-laboratory Reproducibilitymentioning
confidence: 98%
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“…Integrating both of these endpoints into routine toxicology studies and short-term multi-endpoint genetic toxicology studies provides measures of gene mutation frequency as well as clastogenic and aneugenic activity [Dertinger et al, 2010; Bhalli et al, 2011; Cammerer et al, 2011; Shi et al, 2011; Stankowski et al, 2011; Lynch et al, 2011a; Lemieux et al, 2011]. This has led the ICH M7 Guideline [2014] to describe the assay as a suitable system for following-up in vitro mutation positive results.…”
Section: Introductionmentioning
confidence: 99%