Metabolic activation capacity of neonatal mice in relation to the neonatalmouse tumorigenicity bioassay

The neonatal mouse tumorigenicity bioassay is a well-developed animal model that has recently been recommended as an alternative tumorigenicity bioass ay by the International Conference on Harmonization (ICH) for Technical Req uirements for the Registration of Pharmaceuticals for Human Use. There are sufficient data to conclude that this animal model is highly sensitive to g enotoxic chemical carcinogens that exert their tumorigenicity through mecha nisms involving the formation of covalently bound exogenous DNA adducts tha t lead to mutation. On the other hand, it is not sensitive to chemical carc inogens that exert tumorigenicity through a secondary mechanism. The metabolizing enzymes present in the neonatal mouse, particularly the cy tochromes P450, are critical factors in determining the tumorigenic potency of a chemical tested in this bioassay. However, compared to the metabolizi ng enzymes of the adult mouse and rat, the study of the metabolizing enzyme s in neonatal mouse tissues has been relatively limited.