Effects of organic solvent vehicles on benzo[a]pyrene metabolism in rabbit lung microsomes |
| |
| Authors: | D M Kontir C A Glance H D Colby P R Miles |
| |
| Affiliation: | 1. Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505, U.S.A.;2. Department of Physiology, West Virginia University, Morgantown, WV 26506, U.S.A.;1. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;3. Department of Biology, Hakim Sabzevari University, Sabzevar, Iran;4. Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran;5. Faculty of Basic Sciences, Hakim Sabzevari University, Sabzevar, Iran;6. Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, UK;7. Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;1. Heinrich-Heine-Universität Düsseldorf, Department of Rheumatology, Moorenstr. 5, 40225 Düsseldorf, Germany;2. Westfälische Wilhelms-Universität Münster, PharmaCampus, Institute of Pharmaceutical and Medicinal Chemistry, Corrensstr. 48, 48149 Münster, Germany;3. Westfälische Wilhelms-Universität Münster, Core Unit Proteomics, Interdisciplinary Center for Clinical Research, Röntgenstr. 21, 48149 Münster, Germany;4. Heinrich-Heine-Universität Düsseldorf, Department of Gynecology, Moorenstr. 5, 40225 Düsseldorf, Germany;1. College of Chemical Engineering, Xinjiang University, Urumqi 830046, PR China;2. QianJiang College, HangZhou Normal University, HangZhou 310018, PR China;3. Northwest Oilfield Company Engineering Technology Research Institute, SINOPEC, Urumqi, 830013, PR China;4. Key Laboratory of Cleaner Transition of Coal & Chemicals Engineering of Xinjiang Uyghur Autonomous Region, Urumqi 830046, PR China;1. Department of Cytokinetics, Institute of Biophysics AS CR, Královopolská 135, 61265 Brno, Czech Republic;2. Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 61137 Brno, Czech Republic;3. Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic |
| |
| Abstract: | ![]()
In order to study the metabolism of benzo[a]pyrene (BP), it must be dissolved in an organic solvent vehicle for delivery to the tissue. We studied the effects of five organic solvent vehicles, i.e. dimethyl sulfoxide (DMSO), acetone, methanol, ethanol, and ethyl acetate, on benzo[a]pyrene hydroxylase activity and the BP metabolite profile in rabbit lung microsomes. Fluorescence detection of 3- and 9-OH-BP was used to evaluate benzo[a]pyrene hydroxylase activity, and the BP metabolite profile was obtained by HPLC analysis. All solvent vehicles inhibited benzo[a]pyrene hydroxylase in a dose-dependent manner. When the smallest volume of each solvent (10 microliter/ml reaction mixture) was employed, the resulting enzyme activities as related to solvent type, from highest to lowest, were DMSO greater than or equal to methanol greater than ethanol greater than or equal to acetone greater than ethyl acetate. HPLC analysis of BP metabolites formed in the presence of the five solvent vehicles showed that production of all metabolites was greatest when DMSO was used and that linearity of product formation was retained longer with DMSO. The metabolites produced when DMSO was used as the solvent were BP-9,10-diol, BP-4,5-diol, BP-7,8-diol, BP-1,6-quinone, BP-3,6-quinone and 3-OH-BP. A similar metabolite profile was obtained when reactions were carried out with methanol as the solvent vehicle, although the magnitude of production was less than with DMSO. When acetone was used, there were greater amounts of BP-4,5-diol and BP quinone formation and lesser amounts of 3-OH-BP formed than with DMSO or methanol. When ethanol or ethyl acetate was used as a solvent, BP-9,10-diol and 3-OH-BP were the only metabolites produced. These results indicate that all solvent vehicles studied inhibit benzo[a]pyrene hydroxylase from rabbit lung microsomes in a dose-dependent manner and that the magnitudes and types of metabolites formed are highly dependent upon the specific solvent used as the vehicle. The study also indicates that DMSO is probably the solvent vehicle of choice for study of BP metabolism in rabbit lung microsomes. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
