Evidence map›Paper›PMID 29385624›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2018

Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells.

Xiaoqing Guo, Ji-Eun Seo, Steven M Bryce, Jenna A Tan, Qiangen Wu, Stacey L Dial, Martha M Moore, Nan Mei

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Mutation accumulation following extended exposure of human HepaRG cells to a genotoxic carcinogen.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025
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  5. Optimized Photoclick (Bio)Resins for Fast Volumetric Bioprinting.Advanced materials (Deerfield Beach, Fla.) · 2021
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  6. Article
  7. Mechanistic Evaluation of Black Cohosh Extract-Induced Genotoxicity in Human Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Article
  8. Article
  9. Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing.Toxicological sciences : an official journal of the Society of Toxicology · 2020
    Article
  10. Detection of Loss of Heterozygosity in Tk-Deficient Mutants from L5178Y TkMethods in molecular biology (Clifton, N.J.) · 2020
    Article
  11. Benchmark Dose Modeling ofToxicological research · 2018
    Review
  12. Article
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

8 authors at 2 institutions in 1 country.

Xiaoqing GuoDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Ji-Eun SeoDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Steven M BryceLitron Laboratories, Rochester, New York 14612.
Jenna A TanDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Qiangen WuDivision of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Stacey L DialDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Martha M MooreDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Nan MeiDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
National Center for Toxicological Research · USLitron Laboratories (United States) · US

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

TEMPO (2, 2, 6, 6-tetramethylphiperidine-1-oxyl) and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In this study, we investigated and quantified the genotoxicity of 4 structurally similar nitroxides, TEMPO and 3 of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity. In addition, the 4 nitroxides caused DNA-strand breakage. The mutagenicity and DNA damaging dose-responses of the test articles were compared using the PROAST benchmark dose software package. The potency ranking of the 4 nitroxides for mutagenicity was different from the ranking of the DNA damaging effects. The mode of action analysis by a multi-endpoint DNA damage pathway assay classified all 4 nitroxides as clastogens. In addition, the majority of the induced Tk mutants showed loss of heterozygosity at the Tk and D11Mit42 loci (ie, chromosome damage <31 Mbp). These results suggest that TEMPO and its 3 derivatives are cytotoxic and mutagenic in mouse lymphoma cells through a mechanism that involves strand breakage and large alterations to DNA. The potency rankings indicate that the different TEMPO derivatives vary in their mutagenic and DNA damaging potential.

Indexed as

DNA DamageAnimalsCell Line, TumorCell ProliferationCell SurvivalComet AssayCyclic N-OxidesHumansHydroxylamineMiceMutagensPiperidines4-methoxy-2,2,6,6-tetramethylpiperidinyl-1-oxy4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxylCyclic N-OxidesHydroxylamineMutagensPiperidinesTEMPOTEMPOL-H

Identifiers

PMID29385624
PMCPMC6388407
OpenAlexW2791905320

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.