Metabolic activation capacity of neonatal mice in relation to the neonatal mouse tumorigenicity bioassay.
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.
Fu
P P
PP
National Center for Toxicological Research, Jefferson, Arkansas 72079, USA.
Von Tungeln
L S
LS
Hammons
G J
GJ
McMahon
G
G
Wogan
G
G
Flammang
T J
TJ
Kadlubar
F F
FF
D000818:Animals; D000831:Animals, Newborn; D001711:Biotransformation; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018736:DNA Adducts; D006801:Humans; D051379:Mice; D051381:Rats; D018631:ras Proteins / Q000096:biosynthesis
D002273:Carcinogens; D018736:DNA Adducts; D003577:Cytochrome P-450 Enzyme System; D018631:ras Proteins