Resistance to Cyp3a induction by polychlorinated biphenyls, including non-dioxin-like PCB153, in gills of killifish (Fundulus heteroclitus) from New Bedford Harbor

Malin C Celander,Jared V Goldstone,Nadja R Brun,Bryan Clark,Saro Jayaraman,Diane Nacci,John J Stegeman

doi:10.1016/j.etap.2020.103580

Abstract

Previous reports suggested that non-dioxin-like (NDL) PCB153 effects on cytochrome P450 3A (Cyp3a) expression in Atlantic killifish (Fundulus heteroclitus) gills differed between F0 generation fish from a PCB site (New Bedford Harbor; NBH) and a reference site (Scorton Creek; SC). Here, we examined effects of PCB153, dioxin-like (DL) PCB126, or a mixture of both, on Cyp3a56 mRNA in killifish generations removed from the wild, without environmental PCB exposures. PCB126 effects in liver and gills differed between populations, as expected. Gill Cyp3a56 was not affected by either congener in NBH F2 generation fish, but was induced by PCB153 in SC F1 fish, with females showing a greater response. PCB153 did not affect Cyp3a56 in liver of either population. Results suggest a heritable resistance to NDL-PCBs in killifish from NBH, in addition to that reported for DL PCBs. Induction of Cyp3a56 in gills may be a biomarker of exposure to NDL PCBs in fish populations that are not resistant to PCBs.

Highlights

Polychlorinated biphenyls (PCBs) are persistent legacy pollutants abundant in many parts of the world
As expected, when compared to vehicle control, cytochrome P450 1A (Cyp1a) mRNA levels were significantly induced in gills in F1 generation fish from Scorton Creek (SC) treated with the DL congener PCB126 (F(3, 65) = 6.92; adjusted p = 0.017) as well as in fish treated with the PCB126/153 mixture
No changes in Pxr or Cyp3a56 mRNA levels were observed in gills in F2 generation New Bedford Harbor (NBH) killifish treated with the either NDL PCB153, the DL PCB126, or a mixture of the two congeners compared to vehicle control

Summary

Introduction

Polychlorinated biphenyls (PCBs) are persistent legacy pollutants abundant in many parts of the world. In contrast to the DL PCBs, the molecular effects of non-dioxin-like PCBs (NDL PCBs) in fish are less well known, despite the fact that they are vastly more abundant in the environment. This study addresses the molecular effects of the NDL PCBs including an exposure biomarker, and a possible mo lecular adaptation to high levels of NDL PCBs, in the estuarine fish model, Atlantic killifish (Fundulus heteroclitus). Killifish in NBH have evolved a heritable resistance to the effects of DL PCBs, including little or no induction of Cyp1a by DL PCBs or other Ahr agonists (Bello et al, 2001; Nacci et al, 1999). Despite severely high body-burdens of PCBs, the NBH killifish population survive and reproduce, which implies that they have developed a resistance to the adverse effects of NDL PCBs in addition to DL PCBs. the molecular mechanisms involved in PCB resistance are not known

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