DNA double strand break repair as cellular response to genotoxic asarone isomers considering phase I metabolism

Area of Science:

• Environmental toxicology
• Molecular toxicology
• Carcinogenesis research

Background:

• Phenylpropenes, including α-asarone and β-asarone, are found in Acorus calamus.
• Both isomers are recognized as rodent carcinogens.
• The genotoxic mechanisms underlying asarone carcinogenicity remain unclear.

Purpose of the Study:

• To investigate the genotoxic effects of asarone isomers and their phase I metabolites.
• To elucidate the metabolic activation pathways contributing to asarone carcinogenicity.
• To explore the DNA repair mechanisms involved in asarone-induced DNA damage.

Main Methods:

• In vitro incubation of compounds with cells.
• Assessment of DNA strand breaks and micronuclei formation.
• Analysis of DNA double-strand break repair pathways (homologous recombination and non-homologous end joining).

Main Results:

• Asarone metabolites significantly increased DNA strand breaks after 1-hour incubation.
• All tested compounds acted as aneugens, elevating micronuclei levels.
• A decrease in DNA damage was observed after 24-hour incubation, suggesting repair processes.
• Asarone epoxide-induced DNA strand breaks were repaired through homologous recombination.

Conclusions:

• Metabolic activation of asarone isomers is crucial for their genotoxic and carcinogenic effects.
• Asarone metabolites induce aneugenic effects and DNA damage, contributing to their carcinogenic potential.
• The study highlights the role of homologous recombination in repairing DNA damage caused by asarone epoxide.