Pentachlorophenol treatment in vivo elevates point mutation rate in zebrafish p53 gene

Yin, D., Gu, Y., Li, Y., Wang, X., and Zhao, Q.
Mutation research   609(1): 92-101 (Journal)
Registered Authors
Zhao, Qingshun
Pentachlorophenol, Point mutation, Zebrafish, p53 Gene, Acute toxic treatment, Genotoxicity
MeSH Terms
  • Animals
  • Base Sequence
  • Chromatography, High Pressure Liquid/methods
  • DNA/chemistry
  • DNA/genetics
  • DNA Mutational Analysis
  • Dose-Response Relationship, Drug
  • Fish Proteins/genetics
  • Insecticides/toxicity
  • Liver/drug effects
  • Liver/metabolism
  • Molecular Sequence Data
  • Pentachlorophenol/toxicity*
  • Point Mutation/drug effects*
  • Point Mutation/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Toxicity Tests, Acute
  • Transition Temperature
  • Tumor Suppressor Protein p53/genetics*
  • Zebrafish/genetics*
16904934 Full text @ Mutat. Res.
Pentachlorophenol (PCP), a probable human carcinogen, has been heavily used as an aseptic and a biocide throughout the world, and is widely present in the environment. Recent survey in Germany revealed that the average PCP amount in the urine of general German populations was 1.04mug/L while the peak concentration could reach up to 19.1mug/L. PCP was reported to cause DNA damage, but whether it can be involved in inducing point mutations in genome is unknown. To determine the genotoxicity of PCP on vertebrate, we first performed acute toxicity test on zebrafish for the effect of PCP exposure. The LC(50) values of zebrafish exposed to PCP at 24, 48, 72 and 96h were determined to be 0.196, 0.130, 0.130 and 0.130mg/L, respectively. We then treated zebrafish with PCP for 10 days at 0 (control), 0.5, 5 and 50mug/L, respectively, to determine whether PCP could be involved in inducing point mutations. Employing denaturing high-performance liquid chromatography analysis and DNA sequencing, we demonstrated that exposure of PCP to zebrafish at a concentration as low as 5mug/L for 10 days elevates point mutation rate in p53 gene in liver cells. This is the first direct evidence revealing that PCP can elevate point mutation rate in the vertebrate genomes. The result implies PCP might be involved in carcinogenesis by elevating point mutation rate in the somatic genomes.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes