Mapping of phenytoin-inducible cytochrome P450 immunoreactivity in the mouse central nervous system.

The distribution of phenytoin-inducible cytochrome P450 in non-treated mouse brain and spinal cord was analysed immunohistochemically using polyclonal antibodies against phenytoin-induced mouse cerebral microsomal P450. This P450 protein was proved in Ouchterlony [Volk B. et al.

Comparison of enzyme phenotypes in human bladder tumours and experimentally induced hyperplastic and neoplastic lesions of the rat urinary bladder. A combined histochemical and immunohistochemical approach.

The expression of a number of enzymes involved in drug metabolism, membrane function etc. was compared in hyperplastic and neoplastic lesions of the rat bladder and in human bladder tumours. Transitional cell carcinomas (TCC) in both rat and Man were characterized by decreased alkaline phosphatase (ALP) and increased gamma-glutamyl transpeptidase (GGT), beta-glucuronidase (beta-G1), succinate dehydrogenase (SD) and glucose-6-phosphate dehydrogenase (G6PD) activities.

Effect of nutritional imbalances on cytochrome P-450 isozymes in rat liver.

Male Sprague-Dawley rats were fed for six weeks either a control diet containing 22% casein (C) and 5% fat (F) or a low-protein diet (6% C, 5% F) or high-lipid diet (30% C, 30% F). A group of rats received a control diet containing 50 ppm of Phenoclor DP6. Three major forms of cytochrome P-450, UT 50, BP 3a and MC 2 were purified from livers of DP6-fed rats and only two forms, UT 50 and PB 3a, were purified from control and dietary groups.

Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions.

The expression of A and P forms of glutathione S-transferase (GST-A and P), two cytochrome P-450 isoenzymes (P-450 PB3a and P-450 MC2), microsomal epoxide hydrolase (mEHb), glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltranspeptidase (gamma-GT) was compared in preneoplastic liver lesions and background parenchyma of F344 rats post-treated with butylated hydroxyanisole (BHA), ethoxyquin (EQ) or acetaminophen (AAP). These latter three compounds have been shown to inhibit hepatocarcinogenesis after initial treatment with N-ethyl-N-hydroxyethylnitrosamine (EHEN) and a significant decrease in the number of enzyme-altered foci and nodules positive for GST-P, GST-A, G6PD and gamma-GT and negative for P-450 PB3a, P-450 MC2 was associated with their administration. Whereas in the foci case the decrease was most prominent for non-discrete (heterogeneous) type lesions, the results of quantitation of nodules revealed a most significant alteration in the discrete homogeneously staining population.

First evidence of cytochrome P-450 induction in the mouse brain by phenytoin.

Long-term administration of phenytoin (60 mg/kg) to male C57Bl/6J mice causes an average drug serum level of 16-19 micrograms/ml. Cytological changes consisting of focal axonal swellings in the deep cerebellar nuclei are characterized by an increasing accumulation of vesiculotubular membranes in the dense, but ribosome-deficient axoplasm. Microsomal fractions of brain and liver were prepared at intervals until the 80th day of treatment to determine their cytochrome P-450 activities and isoenzyme characteristics.