Evidence map›Paper›PMID 40319998›Full record

ArticleChemico-biological interactions2025

Comparative DNA damage induced by eight nitrosamines in primary human and macaque hepatocytes.

Ji-Eun Seo, Xiaobo He, Matthew Bryant, Aisar H Atrakchi, Timothy J McGovern, Karen L Davis Bruno, Robert H Heflich, Xiaoqing Guo

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemico-biological interactions, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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
    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.

Ji-Eun SeoDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA; Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA. Electronic address: Jieun.Seo@fda.hhs.gov.
Xiaobo HeOffice of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.
Matthew BryantOffice of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.
Aisar H AtrakchiCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Timothy J McGovernCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Karen L Davis BrunoCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Robert H HeflichDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.
Xiaoqing GuoDivision of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA. Electronic address: Xiaoqing.Guo@fda.hhs.gov.

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

N-nitrosamines have been increasingly detected in human drugs, raising serious safety concerns due to their potential mutagenicity and carcinogenicity. In order to expand upon the human data available on these drug impurities, we previously used metabolically competent HepaRG human hepatoma cells to evaluate the genotoxicity of eight small-molecule nitrosamines [N-cyclopentyl-4-nitrosopiperazine (CPNP), N-nitrosodibutylamine (NDBA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosodiisopropylamine (NDIPA), N-nitrosoethylisopropylamine (NEIPA), N-nitroso-N-methyl-4-aminobutyric acid (NMBA), and N-nitrosomethylphenylamine (NMPA)]. In this study, we used the comet assay to further investigate the DNA damage induced by the eight nitrosamines in primary human hepatocytes (PHHs) from three individual donors and primary macaque hepatocytes (PMHs) from freshly isolated livers of six rhesus macaques. In addition, expression of genes encoding Phase I and II metabolic enzymes and the activities of the enzymes were compared in PHHs and PMHs, and Western blot was used to analyze protein biomarkers of DNA damage and apoptosis in PMHs. All eight nitrosamines induced significant DNA damage in both PHHs and PMHs; with the exception of NDMA, higher fold increases in % tail DNA were detected in PMHs compared to PHHs. Greater interindividual variability in CYP gene expression, enzyme activities, and DNA damage responses was observed in PHHs compared to PMHs. Benchmark concentration (BMC) modeling analysis showed that PHHs had more conservative BMC

Indexed as

DNA DamageHepatocytesNitrosaminesAnimalsCells, CulturedComet AssayCytochrome P-450 Enzyme SystemHumansMacaca mulattaMaleCytochrome P-450 Enzyme SystemNitrosaminesDNA damageNitrosaminesPrimary human hepatocytesPrimary macaque hepatocytes

Identifiers

PMID40319998
PMCPMC12441990

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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.