title: Differential sensitivity to pro-oxidant exposure in two populations of killifish (Fundulus heteroclitus).
abstract: New Bedford Harbor (MA, U.S.A.; NBH) is a Superfund site inhabited by Atlantic killifish (Fundulus heteroclitus) with altered aryl hydrocarbon receptor (Ahr) signaling, leading to resistance to effects of polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The Ahr is a transcription factor that regulates gene expression of many Phase I and II detoxifying enzymes and interacts with Nrf2, a transcription factor that regulates the response to oxidative stress. This study tested the hypothesis that PCB-resistant killifish exhibit altered sensitivity to oxidative stress. Killifish F(1) embryos from NBH and a clean reference site (Scorton Creek, MA, U.S.A.; SC) were exposed to model pro-oxidant and Nrf2-activator, tert-butylhydroquinone (tBHQ). Embryos were exposed at specific embryonic developmental stages (5, 7, and 9 days post fertilization) and toxicity was assessed, using a deformity score, survival, heart rate, and gene expression to compare sensitivity between PCB -resistant and -sensitive (reference) populations. Acute exposure to tBHQ resulted in transient reduction in heart rate in NBH and SC F(1) embryos. However, embryos from NBH were more sensitive to tBHQ, with more frequent and severe deformities, including pericardial edema, tail deformities, small body size, and reduced pigment and erythrocytes. NBH embryos had lower basal expression of antioxidant genes catalase and glutathione-S-transferase alpha (gsta), and upon exposure to tBHQ, exhibited lower levels of expression of catalase, gsta, and superoxide dismutase compared to controls. This result suggests that adaptation to tolerate PCBs has altered the sensitivity of NBH fish to oxidative stress during embryonic development, demonstrating a cost of the PCB resistance adaptation.
authors: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
authors: Rachel C
authors: RC
authors: Harbeitner
authors: Mark E
authors: ME
authors: Hahn
authors: Alicia R
authors: AR
authors: Timme-Laragy
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000222:Adaptation, Physiological; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D023781:Fundulidae / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006873:Hydroquinones / Q000633:toxicity*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase; D013997:Time Factors
chemical_list: D029941:Fish Proteins; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D016877:Oxidants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C018855:2-tert-butylhydroquinone; D011078:Polychlorinated Biphenyls; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase