PUBLICATION

MNNG-induced mutations in the adult gill and hepatopancreas and in embryos of rpsL transgenic zebrafish

Authors
Amanuma, K., Nakamura, T., and Aoki, Y.
ID
ZDB-PUB-041021-4
Date
2004
Source
Mutation research   556(1-2): 151-161 (Journal)
Registered Authors
Amanuma, Kimiko, Aoki, Yasunobu
Keywords
Transgenic zebrafish; rpsL; MNNG; Mutagenesis
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Dose-Response Relationship, Drug
  • Gills/drug effects*
  • Gills/metabolism
  • Hepatopancreas/drug effects*
  • Hepatopancreas/metabolism
  • Methylnitronitrosoguanidine/toxicity*
  • Mutagens/toxicity*
  • Zebrafish/embryology*
PubMed
15491643 Full text @ Mutat. Res.
Abstract
To evaluate the feasibility of a mutagenicity assay using adult rpsL transgenic zebrafish, 4- to 8-month-old females were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (0, 15 or 30mg/L in a water bath for 2h). At 2 weeks after exposure, MNNG showed a concentration-dependent significant increase in mutant frequency (MF) of 8 x 10(-5), 18 x 10(-5), and 51 x 10(-5), respectively, in the gill. DNA sequencing revealed that 60-74% of the induced mutations were G:C to A:T transitions, consistent with the known mutagenic effects of MNNG. A marginal but significant increase in MF was observed in the hepatopancreas only in the group exposed to 30mg/L, with the induction of some G:C to A:T transitions. A time-course of the appearance of mutations was determined in fish treated with 15mg/L MNNG. In both, the gill and hepatopancreas, a higher MF was observed at 3 weeks than at 2 weeks, suggesting that an expression time of at least 3 weeks is preferable for the assay. When embryos (29h post-fertilization) were exposed to MNNG (0, 50, and 150mg/L) for 1h, MFs increased significantly with an increase in the concentration of MNNG (5 x 10(-5), 40 x 10(-5), and 144 x 10(-5), respectively) at 3 days after exposure. G:C to A:T transitions were the predominant mutations, and these occurred at the same sites in the rpsL gene as in adult tissues. Thus, MNNG induces typical mutations in the gill and hepatopancreas of adult fish, and in embryos, suggesting that the rpsL zebrafish is a useful tool for monitoring genotoxicity caused by water-borne mutagens.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping