4.6 Article

Genotoxicity, oxidative stress and transcriptomic effects of Nitenpyram on human bone marrow mesenchymal stem cells

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 446, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2022.116065

Keywords

Nitenpyram; Micronucleus; Comet assay; Oxidative stress; Transcriptomics

Funding

  1. National Natural Science Foundation of China [21777020]
  2. Fundamental Research Funds for the Central Universities [DUT20LK19]
  3. Program of Introducing Talents of Discipline to Universities [B13012]
  4. Open Project of State Key Laboratory of Urban Water Resource and Environment [ESK202161]
  5. Dalian Point of Care Testing (POCT) Key Laboratory

Ask authors/readers for more resources

The genotoxicity of nitenpyram (NIT) has been evaluated using human bone marrow mesenchymal stem cells (hBMSCs), showing potential genotoxic effects through oxidative stress and dysregulation of various signaling pathways. Although the risk of NIT alone to human health is low, the synergistic or additive effects with other pesticides should be considered.
Despite of the global contamination and ubiquitous exposure to nitenpyram (NIT), little knowledge is available on the adverse effects to human health, with some evidence referring to its genotoxic potency to non-target organisms and esophageal squamous papilloma in rats. Human bone marrow mesenchymal stem cells (hBMSCs) was employed as an in vitro model more relevant to humans to assess the potential genotoxicity of NIT and to understand the underlying mechanisms at cellular and molecular levels. Noncytotoxic concentrations of NIT, 50-2500 mu g/mL, dose-dependently elevated micronucleus (MN) and nuclear bud (NB) frequencies to 8.7-29%o and 15-35%o, respectively. Additional metabolism by rat liver S9 fraction decreased chromosome impairment by 27-52% on MN frequencies and 63-76% on NB frequencies. A commercial NIT product, containing 20% of NIT and 60% of pymetrozine, caused higher cytotoxicity and chromosome impairment in comparison with NIT alone. Expressions of genes responses to DNA damage, ATM, ATR, p53, p21, Bax, H2AX, and GADD45A were disturbed by NIT treatment. Reactive oxygen species (ROS) amount and superoxide dismutase (SOD) activity were enhanced by NIT. Comet assay showed that lower concentrations of NIT, 12.5-100 mu g/mL, induced the DNA damage. Transcriptomic analysis identified 468 differentially expressed genes (p < 0.05, |log2 (Foldchange)| >= 1), from which 22 pathways were enriched. Multiple affected pathways were related to cancer including viral carcinogenesis and bladder cancer. NIT may produce genotoxicity via inducing oxidative stress and deregulating PI3K/Akt, AMPK and mTOR signaling pathways, associated with carcinogenetic potency. While environmental levels of NIT alone may pose little risk to human health, attention should be paid to the health risk arose from the synergistic or additive effects that may exist among NEOs and other types of pesticides.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available