Sub-chronic exposure to 1,1-dichloropropene induces frameshift mutations in lambda transgenic medaka

Area of Science:

• Environmental Toxicology
• Genetics
• Molecular Biology

Background:

• 1,1-Dichloropropene (1,1-DCP) is a water contaminant with structural similarities to known mutagens.
• Previous in vitro studies suggested potential mutagenicity of 1,1-DCP.
• Transgenic fish models offer a viable system for in vivo genotoxicity assessment.

Purpose of the Study:

• To evaluate the in vivo mutagenicity of 1,1-DCP using a transgenic fish model.
• To characterize the types of mutations induced by 1,1-DCP exposure.
• To assess the utility of the lamda transgenic medaka for environmental chemical risk assessment.

Main Methods:

• Sub-chronic exposure of lamda transgenic medaka to varying concentrations of 1,1-DCP for 6 weeks.
• Quantification of mutant frequencies (MF) in the cII target gene in fish livers.
• Analysis of the mutational spectrum, focusing on frameshift mutations.

Main Results:

• Mutant frequencies increased significantly in a dose-dependent manner with 1,1-DCP exposure.
• A 32-fold induction in MF was observed at the highest exposure concentration (16.60 mg/L).
• Mutations were predominantly +1 frameshift mutations, particularly insertions at thiamine and adenine residues, induced 166-fold.

Conclusions:

• This study provides the first in vivo evidence of 1,1-DCP mutagenicity.
• 1,1-DCP induces a characteristic mutational spectrum dominated by +1 frameshifts.
• The lamda transgenic medaka is a valuable tool for identifying and characterizing genetic risks from environmental chemical exposures.