Evidence map›Paper›PMID 21976233›Full record

ArticleEnvironmental and molecular mutagenesis2011

Simultaneous measurement of benzo[a]pyrene-induced Pig-a and lacZ mutations, micronuclei and DNA adducts in Muta™ Mouse.

Christine L Lemieux, George R Douglas, John Gingerich, Souk Phonethepswath, Dorothea K Torous, Stephen D Dertinger, David H Phillips, Volker M Arlt, Paul A White

Open access · bronzeAbstract read
In one paragraph

Article in Environmental and molecular mutagenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
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  3. Metabolic Activation of Benzo[International journal of molecular sciences · 2022
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  16. Benzo(a)pyrene Is Mutagenic in Mouse Spermatogonial Stem Cells and Dividing Spermatogonia.Toxicological sciences : an official journal of the Society of Toxicology · 2016
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 4 countries.

Christine L LemieuxMechanistic Studies Division, Environmental and Radiation Health Sciences Directorate, HECSB, Health Canada, Ottawa, ON, Canada. christine.lemieux@hc-sc.gc.ca
George R Douglas
John Gingerich
Souk Phonethepswath
Dorothea K Torous
Stephen D Dertinger
David H Phillips
Volker M Arlt
Paul A White
Health Canada · CALitron Laboratories (United States) · USInstitute of Cancer Research · GB

Funding

Validation of a Rodent Mutagenicity AssayR44ES018017 · NIEHS · LITRON LABORATORIES, LTD. · PI DERTINGER, STEPHEN D · 2010 to 2012
$1.8M
NIEHS NIH HHS R44ES018017
6 · The paper itself

Abstract

In this study we compared the response of the Pig-a gene mutation assay to that of the lacZ transgenic rodent mutation assay, and demonstrated that multiple endpoints can be measured in a 28-day repeat dose study. Muta™Mouse were dosed daily for 28 days with benzo[a]pyrene (BaP; 0, 25, 50 and 75 mg/kg body weight/day) by oral gavage. Micronucleus (MN) frequency was determined in reticulocytes (RETs) 48 hr following the last dose. 72 h following the last dose, mice were euthanized, and tissues (glandular stomach, small intestine, bone marrow and liver) were collected for lacZ mutation and DNA adduct analysis, and blood was evaluated for Pig-a mutants. BaP-derived DNA adducts were detected in all tissues examined and significant dose-dependent increases in mutant Pig-a phenotypes (i.e., RET(CD24-) and RBC (CD24-)) and lacZ mutants were observed. We estimate that mutagenic efficiency (i.e., rate of conversion of adducts into mutations) was much lower for Pig-a compared to lacZ, and speculate that this difference is likely explained by differences in repair capacity between the gene targets, and differences in the cell populations sampled for Pig-a versus lacZ. The BaP doubling doses for both gene targets, however, were comparable, suggesting that similar mechanisms are involved in the accumulation of gene mutations. Significant dose-related increases in % MN were also observed; however, the doubling dose was considerably higher for this endpoint. The similarity in dose response kinetics of Pig-a and lacZ provides further evidence for the mutational origin of glycosylphosphatidylinositol (GPI)-anchor deficiencies detected in the Pig-a assay.

Indexed as

Mutagenicity TestsAnimalsBenzo(a)pyreneCD24 AntigenData Interpretation, StatisticalDNA AdductsDose-Response Relationship, DrugEndpoint DeterminationLac OperonMaleMembrane ProteinsMiceMice, TransgenicMicronuclei, Chromosome-DefectiveMicronucleus TestsMutagensBenzo(a)pyreneCD24 AntigenCd24a protein, mouseDNA AdductsMembrane ProteinsMutagensphosphatidylinositol glycan-class A protein

Identifiers

PMID21976233
PMCPMC3258540
OpenAlexW1989802276

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Registered trials

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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.