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  • Title: Effects of pyrazole on nitrosodimethylamine demethylase and other microsomal xenobiotic metabolising activities.
    Author: Craft JA.
    Journal: Biochem Pharmacol; 1985 May 01; 34(9):1507-13. PubMed ID: 3994762.
    Abstract:
    Pyrazole administered to immature rats at one day or on four successive days prior to sacrifice increased a microsomal NDMAD with apparent Km 0.04 mM. Aniline hydroxylase activity was also increased by these treatments. Ethoxycoumarin deethylase and amino pyrine demethylase activities were not altered when animals were treated with pyrazole one day prior to sacrifice but were reduced to below control activity when animals were treated for four successive days. All microsomal mono-oxygenases were decreased when animals received a single administration of pyrazole four 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 four 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. These results suggest that pyrazole induces a cytochrome P-450 isoenzyme with high affinity for NDMA but also acts as a suicide inhibitor of the cytochrome.
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