EFFECTS OF PYRAZOLE ON NITROSODIMETHYLAMINE DEMETHYLASE AND OTHER MICROSOMAL XENOBIOTIC METABOLIZING ACTIVITIES

Pyrazole administered to immature rats at 1 day or on 4 successive days prior to sacrifice increased a microsomal NDMAD [nitrosodimethylamine demethylase] with apparent Km 0.04 mM. Aniline hydroxylase activity was also increased by these treatments. Ethoxycoumarin demethylase and aminopyrine demethylase activities were not altered when animals were treated with pyrazole 1 day prior to sacrifice but were reduced to below control activity when animals were treated for 4 successive days. All microsomal monooxygenases were decreased when animals received a single administration of pyrazole 4 days prior to sacrifice and the cytochrome P-450 content of these microsomes was reduced by up to 50%. When microsomes from untreated animals or animals treated for 4 successive days were incubated with pyrazole in the presence of NADPH, cytochrome P-450 content decreased in a time dependent process to a limiting value. The effect was dependent on pyrazole concentration and saturable. Pyrazole seemingly induces a cytochrome P-450 isoenzyme with high affinity for NDMA [nitrosodimethylamine] but also acts as a suicide inhibitor of the cytochrome. [This is significant as nitrosamines, environmental pollutants, are potent carcinogens.].