Toxicology and applied pharmacology, 2011-01, Vol.250 (2), p.170-183
2011
Details
- Autor(en) / Beteiligte
- Titel
- New CYP1 genes in the frog Xenopus (Silurana) tropicalis: Induction patterns and effects of AHR agonists during development
- Ist Teil von
- Toxicology and applied pharmacology, 2011-01, Vol.250 (2), p.170-183
- Ort / Verlag
- Amsterdam: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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), β-naphthoflavone (βNF), 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). βNF 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 βNF 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 μM 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 μM 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0041-008X, 1096-0333eISSN: 1096-0333DOI: 10.1016/j.taap.2010.10.010Titel-ID: cdi_swepub_primary_oai_DiVA_org_uu_289002
- Format
- –
- Schlagworte
- 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), 5-pentachlorobiphenyl (PCB126), 60 APPLIED LIFE SCIENCES, AMPHIBIANS, ANIMALS, Anura, AQUATIC ORGANISMS, AROMATICS, AZAARENES, AZOLES, beta-naphthoflavone (beta NF), beta-Naphthoflavone - administration & dosage, beta-Naphthoflavone - toxicity, Biologi, Biological and medical sciences, Biology, CELL PROLIFERATION, Cell Proliferation - drug effects, CODONS, CONTROL, Cytochrome P-450 Enzyme System - drug effects, Cytochrome P-450 Enzyme System - genetics, Cytochrome P450 1 (CYP1), Dose-Response Relationship, Drug, DYES, Enzyme Induction - drug effects, Female, Gene Expression Regulation, Developmental - drug effects, GENES, Genome, HETEROCYCLIC COMPOUNDS, HOMEOSTASIS, HYDROCARBONS, INDIGO, Indigo Carmine, INDOLES, Indoles - administration & dosage, Indoles - toxicity, LARVAE, Male, Medical sciences, Models, Animal, NATURAL SCIENCES, NATURVETENSKAP, ORGANIC COMPOUNDS, ORGANIC NITROGEN COMPOUNDS, Polychlorinated Biphenyls - administration & dosage, Polychlorinated Biphenyls - toxicity, PROSTAGLANDINS, PYRROLES, Receptors, Aryl Hydrocarbon - agonists, Receptors, Aryl Hydrocarbon - metabolism, SENSITIVITY, SYNTHESIS, Time Factors, TOXICITY, Toxicology, Transthyretin, Up-Regulation - drug effects, VERTEBRATES, Xenopus, Xenopus (Silurana) tropicalis, Xenopus tropicalis, β-naphthoflavone (βNF)