A comparative analysis of select P450 enzymes in uninduced and PB/BNF-induced hamster and rat liver S9

As part of its Nitrosamine Research Program (NRP), HESI’s Genetic Toxicology Technical Committee (GTTC) has supported the publication of a new study evaluating the relative CYP enzyme activities in uninduced and induced hamster and rat liver S9 preparations. This research is critical for assessing the metabolic activation of potentially carcinogenic N-nitrosamine impurities, particularly in the Ames test, which relies on rodent liver S9 for metabolic activation.

Previous Ames test results have shown inconsistencies in detecting mutagenicity for some N-nitrosamines. To address this, both rat and hamster liver S9 preparations were analyzed for their ability to activate N-nitrosamines into their mutagenic forms. Findings confirm that both species exhibit relevant P450 enzyme activities for N-nitrosamine bioactivation. However, hamster liver S9 demonstrated higher overall P450 activity, supporting its recommendation for regulatory genotoxicity testing of N-nitrosamines in vitro.

Read the full publication to learn more about these findings and their implications for regulatory testing.

A comparative analysis of select P450 enzymes in uninduced and PB/BNF-induced hamster and rat liver S9. Evans et al., 2025. Mutation Research – Genetic Toxicology and Environmental Mutagenesis. https://doi.org/10.1016/j.mrgentox.2025.503855

For more information about the GTTC or NRP, please reach out to any of the managers: Connie Chen, Raechel Puglisi or Alexandra Taraboletti.