New CYP1 genes in the frog Xenopus (Silurana) tropicalis: Induction patterns and effects of AHR agonists during development

Journal Article · Sat Jan 15 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.10.010· OSTI ID:21535215

Berg, Cecilia ^[1]; Goldstone, Jared V; Stegeman, John J ^[2]

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1. Dept of Environmental Toxicology, Evolutionary Biology Centre, Uppsala University, Norbyvaegen 18A, 752 36 Uppsala (Sweden)
2. Biology Department, Redfield 3-42 MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543 (United States)

The Xenopus tropicalis genome shows a single gene in each of the four cytochrome P450 1 (CYP1) subfamilies that occur in vertebrates, designated as CYP1A, CYP1B1, CYP1C1, and CYP1D1. We cloned the cDNAs of these genes and examined their expression in untreated tadpoles and in tadpoles exposed to waterborne aryl hydrocarbon receptor agonists, 3,3',4,4',5-pentachlorobiphenyl (PCB126), {beta}-naphthoflavone ({beta}NF), or indigo. We also examined the effects of PCB126 on expression of genes involved in stress response, cell proliferation, thyroid homeostasis, and prostaglandin synthesis. PCB126 induced CYP1A, CYP1B1, and CYP1C1 but had little effect on CYP1D1 (77-, 1.7-, 4.6- and 1.4-fold induction versus the control, respectively). {beta}NF induced CYP1A and CYP1C1 (26- and 2.5-fold), while, under conditions used, indigo tended to induce only CYP1A (1.9-fold). The extent of CYP1 induction by PCB126 and {beta}NF was positively correlated to the number of putative dioxin response elements 0-20 kb upstream of the start codons. No morphological effect was observed in tadpoles exposed to 1 nM-10 {mu}M PCB126 at two days post-fertilization (dpf) and screened 20 days later. However, in 14-dpf tadpoles a slight up-regulation of the genes for PCNA, transthyretin, HSC70, Cu-Zn SOD, and Cox-2 was observed two days after exposure to 1 {mu}M PCB126. This study of the full suite of CYP1 genes in an amphibian species reveals gene- and AHR agonist-specific differences in response, as well as a much lower sensitivity to CYP1 induction and short-term toxicity by PCB126 compared with in fish larvae. The single genes in each CYP1 subfamily may make X. tropicalis a useful model for mechanistic studies of CYP1 functions.

• OSTI ID: 21535215
• Journal Information: Toxicology and Applied Pharmacology, Vol. 250, Issue 2; Other Information: DOI: 10.1016/j.taap.2010.10.010; PII: S0041-008X(10)00395-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMPHIBIANS
CELL PROLIFERATION
CODONS
CONTROL
GENES
HOMEOSTASIS
HYDROCARBONS
INDIGO
LARVAE
PROSTAGLANDINS
SENSITIVITY
SYNTHESIS
TOXICITY
ANIMALS
AQUATIC ORGANISMS
AROMATICS
AZAARENES
AZOLES
DYES
HETEROCYCLIC COMPOUNDS
INDOLES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
VERTEBRATES