Genotoxic effects of 6PPD-quinone on juvenile European seabass (Dicentrarchus labrax): Impacts on DNA replication fidelity and oxidative DNA damage.

Juvenile European seabass (Dicentrarchus labrax) were exposed to environmentally relevant 6PPD-quinone (2.85 µg/L) for five days to evaluate transcriptional, oxidative, and antioxidant responses and histopathology. The liver showed the strongest gene induction: cdc28 (∼75×), bax (48×), spc25 (45×), and hsp70 (42.5×). Kidney responses were moderate, with bax up ∼5.5× and hsp70 and casp9 ∼2×, while pcna, cenpi, cenpf, and cdc28 were downregulated (0.32-0.66×). Spleen and intestine exhibited marked upregulation of spc25, cenpf, cenpi, and bcl2 (up to ∼34.6× and 16×, respectively), whereas trip13, bax, and bcl2 were unchanged in spleen. Gills displayed strong trip13 (∼32.5×) and spc25 (∼13.7×) induction but downregulation of bax and bcl2. Oxidative DNA damage (8-OHdG) increased in all organs except skin, peaking in spleen; N-myc protein rose in spleen. Catalase activity decreased in liver, kidney, and skin but increased in spleen; MDA decreased in most tissues except skin. Histopathology revealed multifocal hepatic necrosis and vacuolation, splenic fibrosis with hemorrhage and lymphoid depletion, intestinal villous sloughing with submucosal inflammation, severe myositis, epidermal desquamation, and gill lamellar damage. In conclusion, short-term exposure to environmentally relevant 6PPD-quinone elicits organ-specific molecular, oxidative, and pathological alterations in juvenile seabass, indicating significant multisystemic toxicity and potential population-level risks and warrants further ecological investigation.