Characterization of the aryl hydrocarbon receptor repressor and a comparison of its expression in Atlantic tomcod from resistant and sensitive populations.
Atlantic tomcod from the Hudson River, USA, are resistant to cytochrome P4501A1 (CYP1A1) mRNA induction and early life stage toxicities induced by coplanar polychlorinated biphenyls (PCBs) or tetrachlorodibenzo-p-dioxins but not polycyclic aromatic hydrocarbons. We sought to determine if basal expression or inducibility of aryl hydrocarbon receptor repressor (AHRR) mRNA is higher in tomcod from the resistant Hudson River population than in those from sensitive populations. Tomcod AHRR cDNA was characterized and its expression quantified in different tissues and life stages of tomcod from the Hudson River, Miramichi River, Canada (sensitive), and among environmentally exposed tomcod from these two sources and the St. Lawrence River, Canada. Phylogenetic analysis revealed that tomcod AHRR falls within the clade of other vertebrate aryl hydrocarbon receptors (AHRs) but is most closely related to the four previously identified AHRR genes. Induction of AHRR mRNA was observed in all tissues of PCB77-treated juvenile tomcod of Miramichi River descent, and expression differed among tissues and was significantly related to levels of CYPIAI mRNA expression. Aryl hydrocarbon receptor repressor mRNA was similarly inducible in F2 embryos of Miramichi and Hudson River descent by benzo[a]pyrene but less by PCB77 in Hudson River offspring. A significant, positive correlation was observed between CYP1A1 mRNA and AHRR mRNA concentrations in environmentally exposed tomcod from the three rivers. We conclude that differences in basal expression or inducibility of AHRR mRNA are not the mechanistic basis of resistance but that levels of AHRR often mirror those of CYP1A1, suggesting that a common AHR pathway-related mechanism may modulate expression of both genes.
Roy
Nirmal K
NK
Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, New York 10987, USA.
Courtenay
Simon C
SC
Chambers
R Christopher
RC
Wirgin
Isaac I
II
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000187:drug effects; D004351:Drug Resistance; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology; D048388:Gadiformes; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009518:New York; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis* / Q000187:drug effects; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000187:drug effects
D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1