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1. Metabolic profiling and in vitro-in vivo extrapolation of furathiocarb in mammalian hepatic microsomes

Author

Khaled Abass, Petri Reponen, Walaa F. Alsanie, Arja Rautio, and Olavi Pelkonen

Subjects
Pesticides, Toxicokinetics, CYP450, In vitro metabolism, Species differences, Risk assessment, Toxicology. Poisons, RA1190-1270
Abstract

Furathiocarb is a carbamate insecticide found in marine ecosystems as well as river water and sediments. The aim of this study was to characterize species differences in the in vitro metabolism of furathiocarb in seven mammalian species (human, monkey, minipig, rat, mouse, dog, rabbit) analyzed by LC-TOF-MS/MS, in order to provide qualitative and quantitative chemical-specific data to enhance toxicological risk assessment. Furathiocarb was mainly biotransformed to carbofuran metabolic pathway via (N-S) bond-cleavage. Two hydroxylated and sulfoxidated metabolites of furathiocarb were also detected (oxidation pathway). No unique human metabolites were detected. The carbofuran metabolic pathway was more predominant than the furathiocarb oxidation pathway in all species studied; differences based on hepatic clearance rates (CLH), were up to 9.4-fold in monkey and 7-fold in rats, while it was 4.3-fold in human. Animal to human differences in the carbofuran pathway are within the default toxicokinetic uncertainty factor, except for mouse (3.9-fold). Our findings on metabolic profiling and in vitro-in vivo extrapolations are helpful for the interpretation of toxicological findings and chemical risk assessment of furathiocarb.

Published
2022
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2. Characterization of furathiocarb metabolism in in-vitro human liver microsomes and recombinant cytochrome P450 enzymes

Author

Khaled Abass, Petri Reponen, Walaa F. Alsanie, Arja Rautio, and Olavi Pelkonen

Subjects
Pesticides, Risk assessment, in-vitro metabolism, Human variability, Cytochrome P450s, LC-MS, Toxicology. Poisons, RA1190-1270
Abstract

Furathiocarb is a carbamate insecticide detected in ecosystems. Its main metabolite carbofuran has been alluded to affect birth outcomes and disturb hormone levels in humans. The metabolism of furathiocarb in humans has not been characterized. The metabolism studies were performed using hepatic microsomes from ten donors and fifteen human cDNA-expressed CYPs. The initial screening and identification of the metabolites were performed by LC-TOF. Quantifications and fragmentations were performed by LC/MS-MS. Furathiocarb was metabolized to eight phase I metabolites via two general pathways, carbofuran metabolic pathway and furathiocarb oxidation pathway. Six metabolites in the carbofuran metabolic pathway (carbofuran, 3-hydroxycarbofuran, 3-ketocarbofuran, 3-keto-7-phenolcarbofuran, 3-hydroxy-7-phenolcarbofuran, and 7-phenolcarbofuran) were identified with the help of authentic standards. The two unidentified metabolites in the furathiocarb oxidation pathway are probably hydroxylated and sulfoxidated derivatives of furathiocarb. The carbofuran metabolic pathway was more predominant than the furathiocarb oxidation pathway, ratios ranged from 24- to 115-fold in a 10-donor panel of hepatic microsomes. On the basis of recombinant CYP studies, the carbofuran pathway was dominated by CYP3A4 (95.9%); contributions by CYP1A2 (1.3%) and CYP2B6 (2.0%) were minor. The minor furathiocarb oxidation pathway was catalyzed by CYP2C19 and CYP2D6 (hydroxylated/sulfoxidated metabolite A) and by CYP3A5, CYP3A4 and CYP2A6 (metabolite B). High and significant correlation between carbofuran metabolic pathway and CYP3A4 marker activities (midazolam-1'-hydroxylation and omeprazole-sulfoxidation) were observed. Ketoconazole, a CYP3A4-inhibitor, inhibited the carbofuran pathway by 32–86% and hydroxylated/sulfoxidated metabolite-B formations by 41–62%. The data suggest that in humans, the carbofuran metabolic pathway is dominant, and CYP3A4 is the major enzyme involved. These results provide useful scientific information for furathiocarb risk assessment in humans.

Published
2022
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3. Why is Research on Herbal Medicinal Products Important and How Can We Improve Its Quality?

Author

Olavi Pelkonen, Qihe Xu, and Tai-Ping Fan

Subjects
Herbal medicinal products, Network pharmacology, Omic tools, Polypharmacology, Traditional chinese herbal medicines, Medicine
Abstract

Research on herbal medicinal products is increasingly published in “Western” scientific journals dedicated primarily to conventional medicines. Publications are concerned mainly not only on the issues of safety and interactions, but also on efficacy. In reviews, a recurring complaint has been a lack of quality studies. In this opinion article, we present the case of Chinese herbal medicines as an example, as they have been extensively used in the global market and increasingly studied worldwide. We analyze the potential reasons for problems and propose some ways forward. As in the case of any drug, clinical trials for safety, efficacy, and/or effectiveness are the ultimate demonstration of therapeutic usefulness of herbal products. These will only make scientific sense when the tested herbal products are authentic, standardized, and quality controlled, if good practice guidelines of evidence-based medicine are followed, and if relevant controls and outcome measures are scientifically defined. Herbal products are complex mixtures, and for such complexity, an obvious approach for mechanistic studies is network pharmacology based on omic tools and approaches, which has already begun to revolutionize the study of conventional drugs, emphasizing networks, interactions, and polypharmacological features behind the action of many drugs.

Published
2014
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4. Contributors

Author

Arturo Anadón, Vellareddy Anantharam, Anthony E. Archibong, Irma Ares, Adam D. Aulbach, Nikee Awasthee, Aryamitra Banerjee, Leah D. Banks, Frank A. Barile, Sudheer R. Beedanagari, Charalampos Belantis, Enrico Bergamaschi, Sadikshya Bhandari, Sneha P. Bhatia, Karyn Bischoff, David J. Borts, Emily Brehm, Subash Chandra Gupta, Saurabh Chatterjee, Catheryne Chiang, Anirudh J. Chintalapati, P. Cohn, Robert W. Coppock, Lucio G. Costa, Tirupapuliyur V. Damodaran, Clinton D'Souza, Wolf-D. Dettbarn, Amy A. Devlin, Robin B. Doss, Shiwangi Dwivedi, Margitta M. Dziwenka, Jorge Estévez, Daniel S. Fabricant, A.M. Fan, Vanessa A. Fitsanakis, John Flaskos, Jodi A. Flaws, Swaran J.S. Flora, Sue M. Ford, Jessica S. Fortin, Domniki Fragou, Shayne C. Gad, Bianca Galateanu, Dale R. Gardner, George Georgiadis, Fernando Gil, Saryu Goel, Mary Gulumian, P.K. Gupta, Ramesh C. Gupta, Rekha K. Gupta, Sharon Gwaltney-Brant, Alan J. Hargreaves, Kelly L. Harris, Kenneth J. Harris, Holly E. Hatfield, Wallace A. Hayes, Ioannis Heretis, Antonio F. Hernández, Corey J. Hilmas, Darryl B. Hood, Pasi Huuskonen, Stewart B. Jacobson, Sandra A. James-Yi, Huajun Jin, Jun Kanno, Arthi Kanthasamy, Anumantha G. Kanthasamy, Shilpa N. Kaore, Navinchandra M. Kaore, Bhupendra S. Kaphalia, Vesa Karttunen, Gurjot Kaur, Ravneet Kaur, Prasada Rao S. Kodavanti, Urmila P. Kodavanti, George A. Kontadakis, Gopala Krishna, Priya A. Krishna, Kavya A. Krishna, Maria Kummu, George D. Kymionis, Rajiv Lall, P. Lin, Bommanna G. Loganathan, Jarkko Loikkanen, Marcello Lotti, Michael A. Lynes, Brinda Mahadevan, Jitendra K. Malik, Charalampos Mamoulakis, Jane A. Mantey, María Rosa Martínez-Larrañaga, María Aránzazu Martínez, Charalampos Mavridis, Roger O. McClellan, Vincent P. Meador, Lars Friis Mikkelsen, Dejan Milatovic, Ida R. Miller Mukherjee, Anupama Mukherjee, Pushpinder Kaur Multani, Päivi Myllynen, Kirsi Myöhänen, Rekek Negga, Carolina Negrei, Meliton N. Novilla, Stephanie Padilla, Carlos M. Palmeira, Kip E. Panter, Markku Pasanen, Daniel J. Patrick, Sofia Pavanello, Henrik Duelund Pedersen, Olavi Pelkonen, Michael A. Pellizzon, Jason Pitt, Argyro Plaka, Aramandla Ramesh, Saniya Rattan, Jenni Repo, Matthew R. Ricci, Anabela P. Rolo, Magdalini Sachana, Heidi Sahlman, Nitin Saini, Vandana Saini, Kai Savolainen, Ratanesh Kumar Seth, Abha Sharma, Anurag Sharma, Elina Sieppi, Rui Silva, Anita Sinha, Iordanis Skamagkas, Samantha J. Snow, Miguel A. Sogorb, Ajay Srivastava, Szabina A. Stice, Markus Storvik, David T. Szabo, João S. Teodoro, Aristidis M. Tsatsakis, John Tsiaoussis, Kirsi Vähäkangas, Sumit Singh Verma, Eugenio Vilanova, Suryanarayana V. Vulimiri, Genoa R. Warner, Kevin D. Welch, Christina Wilson-Frank, S.H. You, Snjezana Zaja-Milatovic, Ioannis E. Zisis, and Csaba K. Zoltani

Published
2019

5. Biomarkers of Toxicity in Human Placenta

Author

Päivi Myllynen, Heidi Sahlman, Maria Kummu, Pasi Huuskonen, Kirsi Myöhänen, Markus Storvik, Kirsi Vähäkangas, E. Sieppi, Markku Pasanen, Jarkko Loikkanen, Vesa Karttunen, Olavi Pelkonen, and Jenni K. Repo

Subjects
Fetus, biology, Pharmacology, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Biochemistry, Placenta, embryonic structures, Toxicity, biology.protein, medicine, Epigenetics, Aromatase, Xenobiotic, Drug metabolism, Hormone
Abstract

Nutrient and gas exchange between mother and fetus and production of hormones sustaining fetal development are important placental functions carried out by a rich selection of transporter proteins and a variety of metabolizing enzymes. The same proteins handle many xenobiotics which in placenta may pass, accumulate, and change placental functions, causing toxicity. Because of structural and functional variation between species, human placental tissue and human trophoblastic cell lines are the most used systems in the search for placental biomarkers of toxicity. They would be helpful in evaluation of drug toxicity in placenta, and in toxicological risk assessment. Only a few exist so far, e.g. changes in CYP19A1/aromatase by hormonally active compounds, metallothioneins in metal exposure, and level of PAH-DNA adducts associated with fetotoxicity. New possibilities are provided, e.g. by the emerging field of placental epigenetics. Use of placenta and placental biomarkers in regulatory toxicology also awaits further data.

Published
2019

6. List of Contributors

Author

Angela Aliberti, Patrick Allard, Arturo Anadón, Vellareddy Anantharam, Anthony E. Archibong, Adam D. Aulbach, Aryamitra Banerjee, Leah D. Banks, Frank A. Barile, Sudheer R. Beedanagari, Enrico Bergamaschi, Sneha P. Bhatia, Karyn Bischoff, Víctor Castellano, Daniel T. Chang, James J. Chen, Deborah Citrin, Rory Conolly, R.W. Coppock, Lucio G. Costa, T.V. Damodaran, Kellye K. Daniels, Curtis C. Dary, Robin B. Doss, Filipe V. Duarte, Margitta M. Dziwenka, Stephen Edwards, Jorge Estévez, Daniel S. Fabricant, Anna M. Fan, Ali Faqi, Suzanne E. Fenton, Vanessa A Fitsanakis, John Flaskos, Swaran J.S. Flora, Sue M. Ford, Domniki Fragou, Shayne C. Gad, Niels-Christian Ganderup, Dale R. Gardner, Ronette Gehring, Fernando Gil, Saryu Goel, Michael-Rock Goldsmith, Christopher M. Grulke, Mary Gulumian, P.K. Gupta, Ramesh C. Gupta, Sharon Gwaltney-Brant, Alan J Hargreaves, Kelly L. Harris, Holly E. Hatfield, Diane E. Heck, Antonio F. Hernández, Corey J. Hilmas, Evangelia Hondroulis, Darryl B. Hood, Kathryn Hudak, Pasi Huuskonen, Stewart B. Jacobson, Huajun Jin, Laurie B. Joseph, Jun Kanno, Anumantha G. Kanthasamy, Arthi Kanthasamy, Navinchandra M. Kaore, Shilpa N. Kaore, Bhupendra S. Kaphalia, Vesa Karttunen, Greer E. Kaufman, Ravneet Kaur, Hong Duck Kim, Prasada Rao S. Kodavanti, Urmila P. Kodavanti, George A. Kontadakis, Péter Krajcsi, Gopala Krishna, Kavya A. Krishna, Maria Kummu, George D. Kymionis, Michelle A. Lasher, Chen-zhong Li, Wei-Jiun Lin, Bommanna G. Loganathan, Jarkko Loikkanen, Anna E. Lokshin, Marcello Lotti, Tzu-Pin Lu, Yi Lu, Chikezie Madu, Rémi Magnan, Brinda Mahadevan, Jane A. Mantey, María Rosa Martínez-Larrañaga, Vincent P. Meador, Dejan Milatovic, Pushpinder K. Multani, Päivi Myllynen, Kirsi Myöhänen, Rekek Negga, Jairo Nelson, Brian M. Nolen, Meliton N. Novilla, Stephanie Padilla, Carlos M. Palmeira, Kip E. Panter, Markku Pasanen, Daniel J. Patrick, Sofia Pavanello, Olavi Pelkonen, Claudia Pellacani, Michael A. Pellizzon, Andrew D. Penman, Martin Phillips, Jason Pitt, Argyro Plaka, Aramandla Ramesh, Kausik Ray, Casey E. Reed, Jenni Repo, Matthew R. Ricci, Anabela P. Rolo, Magdalini Sachana, Heidi Sahlman, Nitin Saini, William F. Salminen, Kai Savolainen, Laura K. Schnackenberg, D.T. Selvam, Praveen Sharma, Qiang Shi, Elina Sieppi, Jon Sobus, Miguel A. Sogorb, Melissa Stick, Markus Storvik, David T. Szabo, Yu-Mei Tan, João S. Teodoro, Rogelio Tornero-Velez, Beáta Toth, Aristides M. Tsatsakis, Kirsi Vähäkangas, Deon van der Merwe, Ana T. Varela, Eugenio Vilanova, Suryanarayana V. Vulimiri, Kevin D. Welch, Xi Yang, Snjezana Zaja-Milatovic, and Csaba K. Zoltani

Published
2014

7. Foreword

Author

Olavi Pelkonen

Published
2011

8. Placental Toxicity of Organophosphate and Carbamate Pesticides

Author

Kirsi Vähäkangas, Ramesh C. Gupta, and Olavi Pelkonen

Subjects
Pregnancy, Fetus, Toxicodynamics, Developmental toxicity, Pesticide, Biology, medicine.disease, Bioinformatics, Toxicology, medicine.anatomical_structure, Placenta, embryonic structures, Toxicity, medicine, Toxicokinetics, reproductive and urinary physiology
Abstract

Publisher Summary The chapter provides some background information for the understanding and prediction of what pesticides can, in principle, do to the placenta, and what the placenta does to pesticides. Also, a survey of methodologies employing human placenta as a tool to investigate and predict some aspects of developmental toxicity is presented. Finally, the current knowledge on the toxicokinetics and toxicodynamics of pesticides in the placenta, and how these processes affect the fetus and pregnancy in general is reviewed. Organophosphate (OP) and carbamate (CM) pesticides are widely used and can expose pregnant mothers. The placenta is thus one of the targets for these pesticides, but both also convey deleterious effects to the developing fetus. Although pesticide-induced fetotoxicity has been studied in experimental animals and adverse effects have been observed, there is very little information concerning the toxicokinetic behavior of these pesticides (i.e., penetration, protein binding, distribution, and metabolism) in human placenta. Also, data on toxicodynamic mechanisms and consequences to the developing fetus mainly concern experimental animals, and human data is very scanty. In general, it is of considerable importance to elucidate the role of the placenta in contributing to developmental effects and fetotoxicity. Although there are large gaps in the knowledge of placenta and pesticides, a variety of tools are available with which one may, in principle, obtain useful information for assessing the risks of pesticides to the placenta and developing fetus.

Published
2006

11. LIST OF PARTICIPANTS

Author

Günther Achtert, Moises Agosin., Jorma T. Ahokas, Hans-Jürgen Altmann, Alvito P. Alvares, Pentti I. Arvela, A.J. Baars, Christer Von Bahr, Anne-Marie Batt, Giorgio Belvedere, John R. Bend, Philip Bentley, Anders Berg, Margareta Berggren, Friedrich E. Beyhl, Karl Walter Bock, Irmgard Böttcher, G.S. Boyd, Alasdair M. Breckenridge, G. Brunner, Babette Budczies, Brian Burchell, U. Busch, Jorge Capdevila, Kjell Carlström, Claude Charuel, Arthur K. Cho, Allan H. Conney, Marguerite L. Coomes, M.J. Coon, David Y. Cooper, P.J. Cox, Eva Cremer-Schlede, Donald S. Davies, Marie-Pascale Debey, Helmut Denk, Maurice Dickins, G. Deutschmann, Horst Diehl, Agnès Dietsch, William H. Down, Wilfried Duppel, Karl M. Dus, Erik Dybing, D. Ebel, Anneliese Eben, C.R. Elcombe, Lars Ernster, Ronald W. Estabrook, William E. Fann, Francois Fauran, Erik Fellenius, Michael Franklin, Andreas Garbe, Harry V. Gelboin, J. Gielen, James R. Gillette, Hans R. Glatt, A.J. Glazko, Mario Golan, Roland Gräfström, Theodore E. Gram, I.C. Gunsalus, Jan-Åke Gustafsson, Osmo Hänninen, Richard K. Haroz, Gerhard Heinemeyer, H. Herken, Mala Herzberg, Wolfgang Herzberg, Sigrun Hesse, Alfred Hildebrandt, Masaharo Hirata, P. Hlavica, Harald Hoensch, R.W. Hoffbauer, Johan Högberg, J.L. Holtzman, Heimbert Ihlefeld, Magnus Ingelman-Sundberg, Sten Jakobsson, Rolf Jauch, Elizabeth Jeffery, D. Jerina, Bengt Jernström, Karin Johannesen, Jean-Gil Joly, H.G. Jonen, John Jonsson, Niilo Kärki, G.F. Kahl, Regine Kahl, Laurence Kaminsky, A. Kappas, Ryuichi Kato, Rolf Kaufmann, Helmut Kewitz, Hugo Kexel, Manfred Kiese, Sangduk Kim, Jan Koch-Weser, P. Kremers, David Kupfer, John Chr. Larsen, Matti Lang, John J. Lech, Werner Lenk, Wayne Levin, Charles S. Lieber, Christina Lind, Björn Lindeke, R. Lissner, Klaus Lübke, Mahin D. Maines, G.J. Mannering, Carolyn G. Marlowe, Jukka Marniemi, Marios Marselos, J. Marsh, Bettie Sue S. Masters, Ina E. Mattern, Urs A. Meyer, Michel Mercier, John J. Mieyal, Jerry R. Mitchell, Gertrud Mohn, Peter Moldéus, Maria Moron, Jacqueline Mosser, Robert Mull, Ursula Muller-Eberhard, Skakunthola Narasimhulu, Wolfgang Nastainczyk, Robert Neal, Daniel W. Nebert, K.J. Netter, J. Noordhoek, Raymond F. Novak, Franz Oesch, Kyuichio Okuda, Tsuneo Omura, Sten Orrenius, Terence C. Orton, Beverly Paigen, Kenneth Paigen, D.W. Parke, Andrzey Pawlak, Thomas C. Pederson, Olavi Pelkonen, Julian A. Peterson, Richard M. Philpot, Joseph W. DePierre, Davide Pitré, Jutta Poensgen, G. Powis, Russell A. Prough, Kaija Pyykkö, Joseph James Rafter, Anver Rahimtula, Donald J. Reed, H. Remmer, Slobodan Rendic, Ivar Roots, Otto Rosenthal, Alan Rubin, Hans-Heinrich Ruf, Ryo Sato, John B. Schenkman, M. Scheulen, Heinz Schleyer, H.U. Schmassmann, Eike Schmelz, Jochen Schmid, H.-L. Schmidt, Achim Schmoldt, Klaus Schoene, J. Schoppler, Eric Schreiber, Martin Schulman, Rolf Schulte-Hermann, R. Schüppel, Ingeborg Schuster, Thomas Schwartzkopff, Janeric Seidegard, Helmut Sies, Gérard Siest, Z. Sipal, Stephen G. Sligar, Robert Snyder, Eero A. Sotaniemi, Peter Spitzauer, Hansjürgen Staudinger, A. Stier, Robert Stitzel, Minoru Tanaka, David J. Temple, Cherrie Temple, H.A. Tennekes, Leon C. Terriere, Rolf Teschke, Jean-Paul Thenot, Hjördis Thor, Snorri S. Thorgeirsson, Ronald G. Thurman, Teddy G. Traylor, Patricia S. Traylor, Elisabeth Trifilieff, John C.M. Tsibris, Anders Tunek, Parcor Tuong Chi Cuong, H. Uehleke, Volker Ullrich, Helena Vadi, Kirsi Vähäkangas, Harri Vainio, Kostas P. Vatsis, Elliot S. Vesell, Eila Viljakainen, R. Visser, Manfred Volz, Jean-Pierre Villeneuve, William J. Waddell, Richard M. Welch, Peter Wende, Gemot Wendt, Jürgen Werringloer, Jürgen Weymann, F.J. Wiebel, Roland C. Wolf, Thomas Wolff, Peter Wollenberg, C.S. Yang, Shen K. Yang, Yukio Yasukochi, David W. Yesair, K. Zehnder, Daniel M. Ziegler, and Arno Zimmer

Published
1985

12. THE METABOLISM OF BENZO[a]PYRENE IN CELL CULTURES AND HOMOGENATES FROM DIFFERENT HUMAN FETAL TISSUES

Author

Olavi Pelkonen and Pekka Korhonen

Subjects
chemistry.chemical_compound, Tissue culture, Benzo(a)pyrene, chemistry, Biochemistry, Cell culture, Liver cell, Carcinogen Metabolism, Pyrene, Metabolism, Biology, Carcinogen
Abstract

Benzo(a)pyrene is efficiently metabolised by cells derived from human fetal tissues into known (dihydrodiols, phenols, quinones) and unknown metabolites. Benzo(a)pyrene metabolism in cell cultures does not necessarily represent the activity of aryl hydrocarbon hydroxylase in the original tissue in vitro . The intraindividual variability of benzo(a)pyrene metabolism is only about 15 per cent in liver cell cultures and very large, several fold, in different fibroblast cultures. At least part of the intraindividual variability can be overcome by subculturing fetal fibroblasts. Interindividual variability is 5- to 10-fold, a figure also obtained by others in different human cell and tissue culture systems. When compared to some established cell lines, for instance BS-C-1 or BHK-21, human fetal cell cultures metabolise benzo(a)-pyrene to a comparable extent. Human fetal cells in culture seem to be promising models for studying the significance of carcinogen metabolism in terms of toxicity, mutagenicity and carcinogenicity.

Published
1977

14. OXIDATIVE METABOLISM OF CARCINOGENS BY TROUT LIVER RESULTING IN PROTEIN BINDING AND MUTAGENICITY

Author

Niilo T. Kärki, Jorma T. Ahokas, V. Raunio, Olavi Pelkonen, R. Päkkönen, and K. Rönnholm

Subjects
Aflatoxin, biology, Chemistry, Metabolite, Plasma protein binding, biology.organism_classification, chemistry.chemical_compound, Trout, Mixed Function Oxidase, Biochemistry, polycyclic compounds, Microsome, Pyrene, Carcinogen
Abstract

Protein binding of benzo(α)pyrene and mutagenicity resulting from metabolic activation by trout liver microsomal mixed function oxidase was investigated. The metabolite pattern produced by the relatively active benzo(α)pyrene hydroxylase of trout liver microsomes was established by HPLC and compared with that produced by rat liver microsomes. Three dihydrodiols, quinones and two phenols of benzo(α)pyrene were detected as well as indications of other, unidentified metabolites. The pathway of production of some of the metabolites is apparently via reactive intermediates which bind covalently to protein. Like in the mammalian system the intermediates seem to include epoxides as the inhibition of epoxide hydratase results in a relative increase in covalently bound benzo(α)pyrene. Trout liver microsomal mixed function oxidase results in formation of mutagenic intermediates from benzo(α)pyrene, aflatoxin B1 and 2-acetylaminofluorene.

Published
1977

16. THE DISPOSITION OF BENZO(A)PYRENE IN ISOLATED PERFUSED RAT LUNG

Author

Niilo T. Kärki, Olavi Pelkonen, Kirsi Vähäkangas, and Kaisu Nevasaari

Subjects
medicine.medical_specialty, Lung, chemistry.chemical_compound, medicine.anatomical_structure, Endocrinology, Benzo(a)pyrene, chemistry, Anesthesia, Internal medicine, Methylcholanthrene, Male rats, Breathing, medicine, Pyrene, Cigarette smoke, Perfusion
Abstract

Publisher Summary This chapter discusses the disposition of benzo(a)pyrene (BP) in isolated perfused rat lung. The chapter describes a few experiments in which nonfasted male rats of Sprague–Dawley strain weighing 190–260 g were used. Phenobarbitone (PB) in drinking water was given to one group for 7 days. 3-methylcholanthrene was given to the second group in vegetable oil once a day for 3 days. The third group was exposed to cigarette smoke for 10 min by means of a self-made smoking chamber for 2 days before the day of the perfusions: twice on the first day and once on the second day. For lung preparation, the rats were anaesthetized by urethane. Trachea was cannulated for ventilation and a.pulmonalis for perfusion. 12.5 umol of 3H-benzo(a) pyrene dissolved in 0.25 ml of dimethylsulphoxide was added into the perfusate after an equilibration period of 5 min. The temperature was maintained at 37.5–0.5°C. The effects of methylcholanthrene (MC) and PB pretreatment were studied in 2 h perfusions. The half-life of BP in the perfusions of lungs from MC pretreated rats was about 15 min.

Published
1977

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