title: Liver phase I and phase II enzymatic induction and genotoxic responses of beta-naphthoflavone water-exposed sea bass.
abstract: Sea bass were exposed to 0 (control), 0.1, 0.3, 0.9, and 2.7 microM beta-naphthoflavone (BNF) for 0, 2, 8, and 16 h in order to assess the chronological and concentration relationships between BNF phase I and II biotransformation responses, such as liver cytochrome P450 (P450) content, ethoxyresorufin-O-deethylase (EROD), uridine diphosphate-glucuronosyl transferase (UDP-GT), and the genotoxic effects, measured either by erythrocytic micronuclei (EMN) or erythrocytic nuclear abnormalities (ENA) tests. Liver alanine aminotransferase (ALT) activity and liver somatic index (LSI) were also measured. A significant liver EROD activity was found at 8 h exposure, respectively, to 0.1, 0.3, 0.9, and 2.7 microM BNF. Maximal liver EROD activity increase was observed at 16 h exposure to 0.9 microM BNF, whereas the highest liver P450 was reached at 8 h exposure to 2.7 microM BNF. Liver UDP-GT activity was significantly increased at 2 h exposure to 0.1 and 0.3 microM BNF and at 8 h exposure to 0.1, 0.3, and 0.9 microM BNF, decreasing at 16 h, for every exposure concentration. Significant ENA increase was observed at 2h exposure, respectively, to 0.3, 0.9, and 2.7 microM BNF. Maximal ENA increase was observed at 16 h exposure to 0.9 microM BNF. The MN was significantly increased at 8 and 16 h exposure, respectively, to 2.7 and 0.9 microM BNF. Liver ALT activity significantly increases at 8 h exposure to 0.1 and 0.3 microM BNF, whereas liver somatic index was significantly increased from 2 to 16 h exposure for every BNF concentration. A slight liver EROD activity increase with a concomitant lack of liver UDP-GT activity is able to induce significant erythrocytic genotoxic effects. Liver UDP-GT high levels are important in sea bass BNF detoxification. However, high liver UDP-GT activity is not enough to prevent the BNF metabolite genotoxic effects on sea bass erythrocytes when liver EROD activity is induced at 2 and 8 h exposure to 0.3 and 0.9 microM BNF. The genotoxic effects measured as EMN and ENA suggest that the balance between the rates of liver BNF reactive and conjugated metabolites seems to be critical.
authors.affiliation: Animal Physiology/Ecotoxicology Sector, University of Aveiro, 3810-193 Aviero, Portugal. gravatoc@bio.ua.pt
authors.forename: C
authors.initials: C
authors.lastname: Gravato
authors.forename: M A
authors.initials: MA
authors.lastname: Santos
mesh_terms: D000818:Animals; D001492:Bass / Q000235:genetics* / Q000502:physiology*; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000494:pharmacology*; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D019324:beta-Naphthoflavone / Q000009:adverse effects* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase