A new toxicity mechanism of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone: Formation of DNA adducts in mammalian cells and aqueous organisms

Jiabin Wu, Guodong Cao, Feng Zhang, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

8 Citations (Scopus)

Abstract

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPDQ), one of the oxidation products of rubber antioxidant 6PPD, has been identified as a novel toxicant to many organisms. However, an understanding of its underlying toxicity mechanisms remained elusive. In this study, we reported that 6PPDQ could react with deoxyguanosine to form one isomer of 3-hydroxy-1, N2-6PPD-etheno-2′-deoxyguanosine (6PPDQ-dG). Next, by employing an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method, we found that 6PPDQ-dG could be detected in genomic DNA from 6PPDQ-treated mammalian cells and Chlamydomonas reinhardtii. We observed positive correlations between concentrations of exogenous 6PPDQ and the amounts of 6PPDQ-dG, and a recovery period after removal of 6PPDQ also led to decreased levels of the adduct in both organisms, which suggested potential repair pathways for this adduct in mammalian cells and unicellular algae. Additionally, we extracted the genomic DNA from tissues of frozen capelin and observed substantial amounts of the adduct in roe and gills, as well as livers at a relatively lower level. These results provided insights into the target organs and tissues that 6PPDQ might accumulate or harm fish. Overall, our study provides a new understanding of the mechanisms of toxicity of 6PPDQ in mammalian cells and aqueous organisms.

Original languageEnglish
Article number161373
Number of pages6
JournalScience of the Total Environment
Volume866
Early online date6 Jan 2023
DOIs
Publication statusPublished - 25 Mar 2023

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

User-Defined Keywords

  • 6PPDQ
  • Aqueous organisms
  • DNA adduct
  • LC-MS

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