Laromustine (VNP40101M, also known as Cloretazine) is a novel sulfonylhydrazine alkylating (anticancer) agent. Laromustine generates two types of reactive intermediates: 90CE and methylisocyanate. When incubated with rat, dog, monkey, and human liver microsomes, [(14)C]laromustine was converted to 90CE (C-8) and seven other radioactive components (C-1-C-7). There was little difference in the me...

Dysregulations of cytochromes P450 (P450s) under liver injury have been extensively studied. However, little is known about the possible reversing effects of hepatoprotective agents, the understanding of which is of great importance in guiding clinical dosage adjustment for patients with liver injury. This study aims to investigate the dysregulation patterns of major P450s in thioacetamide (TAA...

The primary routes of potential human exposure to N-nitrosodiethylamine (NDEA) are ingestion, inhalation, and dermal contact. Air, diet and smoking contribute to potential human exposure at levels of a few μg of NDEA/day. Potential exposure depends on the ability of the nitrosamines to migrate from the product into the body. The first step in the metabolic degradation of NDEA by cytochrome oxid...

Seven dog cytochromes p450 (p450s) were heterologously expressed in baculovirus-Sf21 insect cells. Of all enzymes examined, CYP1A1 exhibited high 7-ethoxyresorufin O-deethylase activity (low Km enzyme, 1 microM). CYP2B11 and CYP3A12 effectively catalyzed the N1-demethylation and C3-hydroxylation of diazepam (and its derivatives), whereas CYP3A12 and CYP2D15 catalyzed exclusively the N- and O-de...

AIMS To investigate the kinetics of CYP-mediated N-demethylation of methadone in human liver microsomes, and examine the role of stereoselectivity and CYP isoforms involved. METHODS The kinetics of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) formation via N-demethylation of rac-, (R)- and (S)-methadone in human liver microsomes prepared from six liver samples were determined by h...

The interaction of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosomethylaniline (NMA) with cytochromes P450 (CYP), CYP2B4, CYP2E1 and CYP3A6, and their metabolism by these enzymes reconstituted with NADPH-CYP reductase in liposomes were studied. Using the difference spectroscopy, the lowest values of spectral dissociation constants (KS) of the binary complex of NDMA and NMA with the en...

Maximum concentrations of microsomal cytochrome P-450 are present in 3-4 day-old mung beans (Phaseolus aureus). On illumination of dark-grown seedlings, cytochrome P-450 and later cytochrome P-450 undergo a rapid decrease in concentration in vivo, with an apparent half-time of about 6 h. Conversely light-grown seedlings, transferred to darkness, show a slow accumulation of cytochrome P-450, dou...

objective(s):cytochrome p-450 1a1 is an important enzyme in the first phase of the metabolism of some carcinogens such as polycyclic aromatic hydrocarbons (pahs), as well as estrogen. the present study evaluates the existence of cyp1a1 polymorphism in a number of breast cancer samples. materials and methods: one hundred breast cancer patients and the same number of healthy controls were analyze...