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The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) decreases cytochrome P-450 (CYP) expression in rat hepatocytes. Because IL-2 increases c-Myc in lymphocytes and because c-myc overexpression represses several genes, we postulated that the IL-2/IL-2R interaction may increase c-Myc and thereby down-regulate CYP in hepatocytes. Cultured rat(More)
The antihypertensive drug dihydralazine may, on rare occasions, cause immunoallergic hepatitis characterized by anti-cytochrome P450 (P450)1A2 autoantibodies. To understand the first steps leading to this immune reaction, we studied the covalent binding fo dihydralazine metabolites to microsomes from rat and human livers. Upon incubation with NADPH and(More)
Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases from colon or rectum carcinomas were(More)
Troleandomycin, a macrolide antibiotic, has been shown to be demethylated and oxidized into a metabolite which forms an inactive complex with the iron(II) of cytochrome P-450. The role of glutathione in the metabolism of troleandomycin was investigated. Administration of troleandomycin (1 mmol X kg-1 p.o.) decreased the concentration of glutathione in the(More)
TGFalpha is a member of the epidermal growth factor (EGF) family with which it shares the same receptor, the EGF receptor (EGFR). Synthesis of TGFalpha and EGFR in reactive astrocytes developing after CNS insults is associated with the differentiative and mitogenic effects of TGFalpha on cultured astrocytes. This suggests a role for TGFalpha in the(More)
Repeated administration of clarithromycin (0.5 mmol.kg-1 p.o. daily for 5 days) to rats increased markedly the same cytochrome P-450 isoenzyme (P-450p) as that induced by troleandomycin. Clarithromycin, however, did not form cytochrome P-450 Fe(II)-metabolite complexes in vitro with microsomes from clarithromycin-treated rats or in vivo after repeated doses(More)
Genetically-controlled drug oxidation capacity was studied using dextromethorphan, an anti-tussive drug, as the test compound in 103 healthy white French subjects (61 males and 42 females). Phenotyping was performed using the metabolic ratio (MR) calculated as MR = 0-10 h urinary output of dextromethorphan/0-10 h urinary output of dextrorphan, after oral(More)
BACKGROUND & AIMS Interleukin (IL) 2 is used in advanced cancers, but its effects on cytochrome P450 remain unknown. Other cytokines down-regulate hepatic cytochrome P450, but it is not known whether this involves cytokine receptors. The aim of this study was to determine whether the IL-2 receptor is expressed on hepatocytes and whether its activation by(More)
BACKGROUND & AIMS A single dose of alcohol causes transient hepatic mitochondrial DNA (mtDNA) depletion in mice followed by increased mtDNA synthesis and an overshoot of mtDNA levels. We determined the effect of repeated alcohol binges on hepatic mtDNA in mice. METHODS Ethanol (5 g/kg) was administered by gastric intubation daily for 4 days, and mtDNA(More)
1. A genetic polymorphism in human erythrocyte thiopurine methyltransferase activity (RBC TPMT) resulting in a trimodal phenotypic distribution has been demonstrated both in a North American population and in British children. 2. We studied whether such a polymorphism may be also present in a white French population by testing RBC TPMT activity in 303(More)