Characterization of Resistance to Halogenated Aromatic Hydrocarbons in a Population of Fundulus heteroclitus from a Marine Superfund Site

摘要

The expression of xenobiotic metabolizing enzymes in Fundulus heteroclitus from New Bedford Harbor and Scorton Creek (SC) were examined. Despite higher polychlorinated biphenyl (PCB) concentrations in NBH than in SC fish - approx. 1500-fold - cytochrome P4501A1 (CYP1A1) expression was not higher in NBH fish than in SC fish. GST activity was higher in the intestines of NBH fish than in any other tissue. 2,3,7,8-Tetrachlorodibenzofuran (TCDF) induced CYP1A1 expression in SC fish. In contrast, NBH fish showed little CYP1A1 induction by any measure. Hepatic GST activity was induced only in male NBH fish. 2,3,7,8-Tetrachlor odibenzo-p-dioxin (TCDD) and Beta-naphthoflavone (BNF) induced CYP1A1 activity to the same level in primary cultures of hepatocytes from SC or NBH fish. However hepatocytes from NBH fish were 14-fold less sensitive to TCDD and 3-fold less sensitive to BNF than hepatocytes from SC fish. To examine the heritability of resistance, NBH and SC F(sub 1) fish were treated with H3-TCDD or BNF. H3-TCDD induced CYP1A1 expression only in SC F(sub 1) fish. BNF induced CYP1A1 expression in both SC and NBH F(sub 1) fish. There was no significant difference in hepatic H3-TCDD concentrations between SC and NBH F(sub 1) fish. Hepatic AhR content, as measured by photoaffinity labeling with I125-N3Br2DD, was lower in NBH fish than in SC fish, but this difference did not persist. These results indicate that NBH Fundulus have developed a pre- translational, systemic, heritable resistance to HAHs and suggest that an alteration in the AhR pathway is responsible for this resistance.