Chronic exposure to the tire-wear contaminant 6-PPDQ induces senescence-associated biomarkers and neurobehavioral deficits: Involvement of ABL1-p53-autophagy signaling.

Authors

Zejiang Ma, Manxue Bai, Chunmei Xia, Jianguang Li, Jian Lu

Published in

Ecotoxicology and environmental safety. Volume 325. Pages 120962. Oct 22, 2026. Epub Oct 22, 2026.

Abstract

While 6-PPD quinone (6-PPDQ) is known for its acute lethality to salmonids, its chronic impacts on non-target species remain elusive. Here, we evaluated the chronic toxicity of 6-PPDQ across multiple biological models. Our results demonstrate that 6-PPDQ exposure significantly curtailed the survival and physiological motility of the nematode Caenorhabditis elegans, while inducing cellular senescence-associated biomarkers and a secretory phenotype (SASP) in human MRC-5 cells. In adult zebrafish, chronic exposure over a 28-month follow-up window precipitated cognitive and neurobehavioral deficits, characterized by impaired spatial learning, elevated agonistic reactivity, and glutamatergic excitotoxicity. Through computational screening, molecular docking, and pharmacological rescue, we identified ABL1 as a prioritized candidate target and functional mediator of 6-PPDQ toxicity. Total ABL1 protein abundance was elevated in exposed zebrafish brains alongside p53 accumulation and autophagic substrate (p62 and LC3-II) retention. Importantly, concurrent treatment with the ABL1 kinase inhibitor nilotinib attenuated p53 induction, restored autophagic flux, and rescued locomotor deficits, implicating the ABL1-associated pathway in these phenotypes. Because overt organismal morbidity was manifest predominantly at upper-bound exposure concentrations (10 µg/L), these phenotypes reflect chronic toxic stress rather than an acceleration of natural aging. These findings identify an ABL1-associated mechanism of chronic neurotoxicity and emphasize the need to assess long-term neurological risks associated with tire-wear pollution.

PMID:
42913102
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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