PUBLICATION

Osteotoxicity of 3-methylcholanthrene in fish

Authors
Laizé, V., Gavaia, P.J., Tarasco, M., Viegas, M.N., Caria, J., Luis, N., Cancela, M.L.
ID
ZDB-PUB-180626-10
Date
2018
Source
Ecotoxicology and environmental safety   161: 721-728 (Journal)
Registered Authors
Cancela, Leonor
Keywords
AHR/PXR signaling pathways, Caudal fin regeneration, Extracellular matrix mineralization, Opercular bone, Osteotoxicity, Skeletal deformities
MeSH Terms
  • Animals
  • Calcification, Physiologic/drug effects
  • Cell Line
  • Humans
  • Larva/metabolism
  • Methylcholanthrene/toxicity*
  • Osteogenesis/drug effects*
  • Receptors, Aryl Hydrocarbon/metabolism
  • Signal Transduction/drug effects
  • Zebrafish/growth & development
  • Zebrafish/metabolism
PubMed
29940513 Full text @ Ecotoxicol. Environ. Saf.
Abstract
Many chemicals produced by human activities end up in the aquatic ecosystem causing adverse developmental and reproductive effects in aquatic organisms. There is evidence that some anthropogenic chemicals disturb bone formation and skeletal development but the lack of suitable in vitro and in vivo systems for testing has hindered the identification of underlying mechanisms of osteotoxicity. Several fish systems - an in vitro cell system to study extracellular matrix mineralization and in vivo systems to evaluate bone formation and skeletogenesis - were combined to collect data on the osteotoxic activity of 3-methylcholanthrene (3-MC), a polycyclic aromatic hydrocarbon. Anti-mineralogenic effects, increased incidence of skeletal deformities and reduced bone formation and regeneration were observed in zebrafish upon exposure to 3-MC. Pathway reporter array revealed the role of the aryl hydrocarbon receptor 2 (Ahr2) in the mechanisms underlying 3-MC osteotoxicity in mineralogenic cell lines. Analysis of gene expression in zebrafish larvae confirmed the role of Ahr2 in the signaling of 3-MC toxicity. It also indicated a possible complementary action of the pregnane X receptor (Pxr) in the regulation of genes involved in bone cell activity and differentiation but also in xenobiotic metabolism. Data reported here demonstrated the osteotoxicity of 3-MC but also confirmed the suitability of fish systems to gain insights into the toxic mechanisms of compounds affecting skeletal and bone formation.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping