METABOLIC ACTIVATION CAPACITY OF NEONATAL MICE IN RELATION TO THE NEONATAL MOUSE TUMORIGENICITY BIOASSAY

Abstract

The neonatal mouse tumorigenicity bioassay is a well-developed animal model that has recently been recommended as an alternative tumorigenicity bioassay by the International Conference on Harmonization (ICH) for Technical Requirements for the Registration of Pharmaceuticals for Human Use. There are sufficient data to conclude that this animal model is highly sensitive to genotoxic chemical carcinogens that exert their tumorigenicity through mechanisms involving the formation of covalently bound exogenous DNA adducts that lead to mutation. On the other hand, it is not sensitive to chemical carcinogens that exert tumorigenicity through a secondary mechanism.

The metabolizing enzymes present in the neonatal mouse, particularly the cytochromes P450, are critical factors in determining the tumorigenic potency of a chemical tested in this bioassay. However, compared to the metabolizing enzymes of the adult mouse and rat, the study of the metabolizing enzymes in neonatal mouse tissues has been relatively limited.

Notes

This paper was refereed by Dr. Anthony Y. H. Lu, Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, N.J.