Evidence map›Paper›PMID 31374128›Full record

ArticleEnvironmental and molecular mutagenesis2019

Bioactivation mechanisms of N-hydroxyaristolactams: Nitroreduction metabolites of aristolochic acids.

Yoshiharu Okuno, Radha Bonala, Sivaprasad Attaluri, Francis Johnson, Arthur P Grollman, Viktoriya S Sidorenko, Yoshimitsu Oda

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Environmental and molecular mutagenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  5. Medicina (Kaunas, Lithuania) · 2023
    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

7 authors at 3 institutions in 2 countries.

Yoshiharu OkunoDepartment of Applied Chemistry and Biochemistry, National Institute of Technology, Wakayama College, 77 Noshima, Nada, Gobo-shi, Wakayama, 644-0023, Japan.
Radha BonalaDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, 11794, USA.
Sivaprasad AttaluriDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, 11794, USA.
Francis JohnsonDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, 11794, USA.
Arthur P GrollmanDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, 11794, USA.
Viktoriya S SidorenkoDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, 11794, USA.
Yoshimitsu OdaInstitute of Life and Environmental Sciences, Osaka Shin-Ai College, 6-2-28 Tsurumi, Tsurumi-ku, Osaka, 538-0053, Japan.
Stony Brook University · USNational College of Technology, Wakayama College · JPTsurumi University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aristolochic acids (AAs) are human nephrotoxins and carcinogens found in concoctions of Aristolochia plants used in traditional medicinal practices worldwide. Genotoxicity of AAs is associated with the formation of active species catalyzed by metabolic enzymes, the full repertoire of which is unknown. Recently, we provided evidence that sulfonation is important for bioactivation of AAs. Here, we employ Salmonella typhimurium umu tester strains expressing human N-acetyltransferases (NATs) and sulfotransferases (SULTs), to study the role of conjugation reactions in the genotoxicities of N-hydroxyaristolactams (AL-I-NOH and AL-II-NOH), metabolites of AA-I and AA-II. Both N-hydroxyaristolactams show stronger genotoxic effects in umu strains expressing human NAT1 and NAT2, than in the parent strain. Additionally, AL-I-NOH displays increased genotoxicity in strains expressing human SULT1A1 and SULT1A2, whereas AL-II-NOH shows enhanced genotoxicity in SULT1A1/2 and SULT1A3 strains. 2,6-Dichloro-4-nitrophenol, SULTs inhibitor, reduced umuC gene expression induced by N-hydroxyaristolactams in SULT1A2 strain. N-hydroxyaristolactams are also mutagenic in parent strains, suggesting that an additional mechanism(s) may contribute to their genotoxicities. Accordingly, using putative SULT substrates and inhibitors, we found that cytosols obtained from human kidney HK-2 cells activate N-hydroxyaristolactams in aristolactam-DNA adducts with the limited involvement of SULTs. Removal of low-molecular-weight reactants in the 3.5-10 kDa range inhibits the formation of aristolactam-DNA by 500-fold, which could not be prevented by the addition of cofactors for SULTs and NATs. In conclusion, our results demonstrate that the genotoxicities of N-hydroxyaristolactams depend on the cell type and involve not only sulfonation but also N,O-acetyltransfer and an additional yet unknown mechanism(s). Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Indexed as

AcetyltransferasesAristolochic AcidsArylamine N-AcetyltransferaseArylsulfotransferaseCarcinogensCell LineDNADNA AdductsHumansMutagensSalmonella typhimuriumSulfotransferasesAcetyltransferasesAristolochic AcidsArylamine N-AcetyltransferaseArylsulfotransferaseCarcinogensDNADNA AdductsMutagensSulfotransferasesaristolactam-DNA adductsHK-2 cytosolsN,O-acetyltransfersulfonationumu test

Identifiers

PMID31374128
PMCPMC6899766
OpenAlexW2965500618

What OpenQuestion holds

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LicenceCC BY
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.