PUBLICATION

Exposure to the heavy metal lead induces DNA copy number alterations in zebrafish cells

Authors
Lee, J., Freeman, J.L.
ID
ZDB-PUB-200623-3
Date
2020
Source
Chemical Research in Toxicology   33(8): 2047-2053 (Journal)
Registered Authors
Freeman, Jennifer
Keywords
none
Datasets
GEO:GSE149382
MeSH Terms
  • Animals
  • Cell Line
  • DNA/drug effects*
  • DNA/genetics
  • DNA Copy Number Variations/drug effects*
  • Fibroblasts/drug effects*
  • Lead/chemistry
  • Lead/toxicity*
  • Zebrafish
PubMed
32567310 Full text @ Chem. Res. Toxicol.
Abstract
DNA copy number variants (CNVs) are associated with the development of complex neurological diseases and disorders including autism spectrum disorder, schizophrenia, Alzheimer's disease, and Parkinson's disease. Exposure to multiple environmental chemicals including various heavy metals is suggested as a risk factor in these neurological diseases and disorders, but few studies have addressed if heavy metal exposure can result in de novo DNA copy number changes as a genetic mechanism contributing to these disease outcomes. In this study to further investigate the relationship between heavy metal exposure and de novo copy number alterations (CNAs), zebrafish fibroblast cells were exposed to the neurotoxicant lead (Pb). A crystal violet assay was first used to determine exposure concentrations with greater than 80% cell confluency. Then a zebrafish-specific array comparative genomic hybridization (CGH) platform was used to detect CNAs following a 72 hour Pb exposure (0.24, 2.4, or 24 μM). The Pb exposure resulted in 72 CNA amplifications ranging in size from 5 to 329 kb. No deletions were detected. CNAs resulted in 15 CNA regions (CNARs), leaving 7 singlet CNAs. Two of the singlets were within high repeat genomic locations. The number of CNAs tended to increase in a concentration dependent manner. Several CNARs encompassed genes previously reported to have altered expression with Pb exposure, suggesting a mechanistic link. In addition, almost all genes are associated within a molecular network with amyloid precursor protein (APP), a key molecular target associated with the pathophysiology of Alzheimer's disease. Overall, these findings show that Pb exposure results in de novo CNAs that could serve as a mechanism driving adverse health outcomes associated with Pb toxicity including neurological disease pathogenesis for further study.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes