Multidimensional bioresponses in nematodes contribute to the antagonistic toxic interaction between pentachlorophenol...

Interactions between nanomaterials (NMs) and coexisting contaminants are important contributors to their joint biological effects, while the reverse actions of bioresponses in determining the toxic interaction between NMs and contaminants were rarely understood. Here, we investigated the toxic interaction and mechanism between TiO₂ NMs (nTiO₂) and pentachlorophenol (PCP) in soil using the model nematode (Caenorhabditis elegans). PCP (0.5-50 mg/kg) and nTiO₂ (50-5000 mg/kg) co-exposures induced antagonistic effects on the survival, growth, and locomotion of nematodes, and the levels of ultrastructural damage and oxidative stress exhibited consistent alterations. Soil PCP concentrations changed insignificantly after the single or combined exposures, indicating a negligible direct interaction between PCP and nTiO₂ under the soil condition. Transcriptomic analysis revealed that after 50 mg/kg PCP exposure, half of differentially expressed genes were involved in epidermal collagen synthesis, while the PCP-nTiO₂ co-exposure particularly activated genes related to antistress responses and the positive regulation of physiological functions. Further biochemical analysis demonstrated the antagonistic interactions were derived from two aspects: 1) PCP-induced epidermal collagen incrassation lowered the bioaccumulation and toxicity of nTiO₂; 2) nTiO₂-activated glutathione detoxification pathway alleviated PCP-induced toxicity. These findings highlight the key role of bioresponses in determining toxic interactions between NMs and co-contaminants.