Evidence for hormesis in mutagenicity dose-response relationships

Area of Science:

• Toxicology
• Genetics
• Biostatistics

Background:

• Hormesis, a dose-response relationship characterized by low-dose stimulation and high-dose inhibition, is a recognized toxicological phenomenon.
• The Ames assay is a standard bacterial reverse mutation test used to assess the mutagenicity of chemicals.
• Understanding dose-response relationships is critical for chemical risk assessment.

Purpose of the Study:

• To evaluate the occurrence of hormetic dose responses across multiple Ames assay tester strains.
• To determine if specific Ames strains are more prone to exhibiting hormetic effects.
• To compare dose-response patterns between strains detecting base-pair substitutions versus frameshift mutations.

Main Methods:

• Re-analysis of 825 chemicals from three published datasets using a five-dose protocol in Ames strains TA97, TA98, and TA100.
• Inclusion of assays with and without metabolic activation (S9 fraction).
• Application of stringent statistical criteria to identify hormetic dose-response patterns.

Main Results:

• 11.5% (95/825) of chemicals met entry criteria for analysis.
• Hormesis was observed in 29.5% (18/61) of assays using the TA100 strain (base-pair substitutions).
• Only 2.2% (1/46) of assays using TA97 and TA98 strains ( અframeshift mutations) met hormesis criteria, suggesting a threshold model.

Conclusions:

• The TA100 Ames assay strain supports a hormetic dose-response model for chemical mutagenicity.
• Ames strains TA97 and TA98, detecting frameshift mutations, are more consistent with a threshold dose-response model.
• These findings highlight strain-specific differences in chemical dose-response behavior within the Ames test system.