Rat liver S9 preparations contain comutagenic activity.

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Rat liver S9 preparations are commonly used in genotoxicity testing.
• UV radiation is a known mutagen, and its effects can be modulated by other substances.
• DNA repair mechanisms are crucial for cellular resistance to mutagenic agents.

Purpose of the Study:

• To investigate the comutagenic activity of rat liver S9 preparations on UV mutagenesis in Escherichia coli.
• To characterize the nature of the comutagenic substance within the S9 fraction.
• To elucidate the role of DNA repair pathways in mediating the comutagenic effect.

Main Methods:

• Exposure of Escherichia coli WP2 strains to UV radiation in the presence of rat liver S9 preparations.
• Comparison of comutagenic activity in wild-type and DNA repair-deficient E. coli strains (uvrA).
• Assessment of the heat-lability and dialyzability of the comutagenic factor.

Main Results:

• Rat liver S9 preparations exhibited significant comutagenic activity, enhancing UV-induced mutagenesis in E. coli WP2.
• This comutagenic effect was dependent on the uvr-dependent excision repair pathway, as repair-deficient strains did not show enhancement.
• The comutagenic substance was found to be heat-labile and non-dialyzable, suggesting a proteinaceous nature.

Conclusions:

• Rat liver S9 contains a proteinaceous comutagen that potentiates UV mutagenesis in E. coli.
• The comutagenic activity is mediated through interaction with or dependence on the bacterial DNA excision repair system.
• This finding differentiates the comutagen from the mutagenic component in S9, which is dialyzable and effective in repair-deficient strains.