Markku J Pasanen

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The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing(More)
In order to survey changes and activities in the polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes implicated in lung cancer susceptibility studies, we investigated enzyme induction by 2–5-ring-sized ‘biomarker’ PAHs in rat liver and lung, and the activities in five human lung specimens. Naphthalene, phenanthrene, pyrene, chrysene, and(More)
Cocaine is hepatotoxic in several species, including man. A high dose of cocaine produces metabolismdependent, mainly pericentral, liver damage. At 24h after a single dose of cocaine, mouse hepatic P450 content decreases but CYP2A activities; coumarin 7-hydroxylase and testosterone 15α-hydroxylase increase concomitant with prominent diffuse cell necrosis.(More)
During past decades, knowledge on placental drug metabolism and mechanisms of placental transfer has increased significantly. Most pharmaceutical drugs administered during pregnancy cross the placenta to some extent. The important properties determining the placental transfer by passive diffusion are molecular weight, pK(a), lipid solubility and protein(More)
In traditional Chinese medicine (TCM), multicomponent and principally plant-derived drugs are used for disease prevention, symptom amelioration and treatment in a personalized manner. Because of their complex composition and consequent multiple targets and treatment objectives, the application of omics techniques and other integrative approaches seems(More)
This study was designed to analyze the effect of environmental oxidative stress on human placental monooxygenases, glutathione S-transferase (GST) activity and polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human term placentas from radioactivity-contaminated and chemically-polluted areas of the Ukraine and Belarus, and to compare these biomarkers to(More)
A method for biological monitoring of urinary 2-(thiocyanomethylthio)benzothiazole (TCMTB), a wood preservative and an industrial chemical, was developed. Three different doses of TCMTB in olive oil were given to male rats by gavage for 3 weeks. Urine was collected daily and the metabolites were analysed as thioethers by derivatization with(More)
Acute effects of a single intraperitoneal dose of allyl alcohol (AA, 64 mg/kg), dimethylnitrosamine (DMNA, 30 mg/kg), hexachlorobutadiene (HCBD, 50 mg/kg), carbon tetrachloride (CCl4, 24 mg/kg), cocaine (60 mg/kg) and pyrazole (300 mg/kg) on the hepatic histology and monooxygenases in DBA/2 and C57B1/6 strains of mice were investigated. All substances(More)
The first step in the oxidative metabolism of cocaine is N-demethylation to norcocaine, which is further N-hydroxylated to more toxic N-hydroxynorcocaine. In this study we examined the kinetics of norcocaine N-hydroxylation mediated by cytochrome P450 (CYP) in mouse and human liver microsomes. N-hydroxynorcocaine was identified by analytical HPLC-MS after(More)