Dioxin resistance in killifish (Fundulus heteroclitus) from New Bedford Harbor, MA

New Bedford Harbor (NBH), MA, is heavily contaminated with halogenated aromatic hydrocarbons (HAHs) including some potent Ah receptor (AhR) agonists. To determine if NBH Fundulus have developed resistance to HAH, we examined the inducibility of cytochrome P4501A1 (CYP1A1) in fish from NBH and Scorton Creek (SC, reference site). In the SC fish CYP1A1 RNA, protein and activity, was induced by 2,3,7,8-tetrachlorodibenzofuran (TCDF) in all tissues examined. In contrast, NBH fish showed little CYP1A1 induction by any measure, in any tissue. To examine the heritability of this resistance, laboratory-reared offspring of NBH and SC fish were treated with [3H]2,3,7,8-tetrachlorodibenzodioxin (TCDD). CYP1A1 was induced in SC offspring, but not in NBH offspring. To investigate the magnitude of this resistance, CYP1A1 was measured in Fundulus primary hepatocyte cultures treated with TCDD or beta-naphthoflavone (BNF). Hepatocytes from NBH fish were 14-fold less sensitive to TCDD than those from SC fish, but only three-fold less sensitive to BNF. These results indicate that chronic exposure to high levels of HAH has produced a heritable reduction in the sensitivity of NBH Fundulus to AhR agonists. These findings suggest an alteration in the AhR signal transduction pathway in the dioxin-resistant NBH fish; this is the subject of continuing research. (NIEHS ESO7381.)