PMID: 6113938May 1, 1981Paper

A comparative study of benzo[a]pyrene hydroxylase and epoxide hydrolase derived from isolated rat hepatic nuclei and microsomes

Drug Metabolism and Disposition : the Biological Fate of Chemicals
L S Gontovnick, G D Bellward

Abstract

Several properties of benzo[a]pyrene hydroxylase (AHH) and epoxide hydrolase (EH) in isolated rat hepatic nuclei were investigated. Comparisons were made with microsomal AHH and EH in order to determine whether the nuclear enzymes were distinct from those of endoplasmic reticulum origin. The ratio of EH to AHH in the nuclei of adult male rats was 4.5 compared to 1.6 in the microsomes. Phenobarbital increased AHH in nuclei from immature males and females. However, the increase were markedly lower than those observed in the microsomes. In contrast, 3-methylcholanthrene increased nuclear AHH to a greater extent than the microsomal enzyme. The age and sex dependence, the inhibition by SKF 525-A, the stimulatory and inhibitory effects of 7,8-benzoflavone and the decrease produced by trans-stilbene oxide administration were the same for both nuclear and microsomal AHH. Phenobarbital, l-alpha-acetyulmethadol, and trans-stilbene oxide increased nuclear EH. The increases were approximately 3-fold lower than observed in the microsomes. EH activity in both nuclei and microsomes was inhibited by 1,2-epoxy-3,3,3-trichloropropane. The data indicate that both the constitutive and induced form(s) of AHH in isolated nuclei and endoplasmic retic...Continue Reading

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