Table Of ContentArchives of Toxicology, Supplement 2
Mechanism of Toxic Action
on Some Target Organs
Drugs and Other Substances
Proceedings of the
European Society of Toxicology
Meeting held in Berlin (West), June 25-28, 1978
Edited by
P. L. Chambers and P. Giinzel
Springer-Verlag Berlin Heidelberg New York 1979
Dr. PHILIP L. CHAMBERS
Dept. of Pharmacology, Trinity College, Dublin 2, Ireland
Dr. PETER GDNZEL
Schering AG, Dept. of Exp. Toxicology, 1000 Berlin-Bergkamen, FRG
With 150 Figures
ISBN-13: 978-3-540-09305-3 e-ISBN-13: 978-3-642-67265-1
DOl: 10.1007/978-3-642-67265-1
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© by Springer-Verlag Berlin Heidelberg 1979
Sofkover reprint of the hardcover 1st edition 1979
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Contents
Young Scientists Award Lecture 1978:
Studies on the Role of Acetylhydrazine in Isoniazid Hepatotoxicity.
J. A. TIMBRELL. With 3 Figures .......................................... .
The Influence of the Neuro-Endocrine System on the Toxic Reactions
Due to Hormones and Other Compounds
Evaluation of Effects of Sexual Steroids on the Hypothalamic-Pituitary System of
Animals and Man.
M. F. EL ETREBY, K.-J. GRAF', P. GiiNZEL, and F. NEUMANN. With 19 Figures... 11
Ultrastructure of Intermediate Lobe of the Pituitary and Melanocyte-Stimulating Hor
mone Secretion in Oestrogen-Induced Kidney Tumors in Male Hamsters.
P. G. SALUJA, J. M. HAMILTON, A. J. THODY, A. A. ISMAIL, and J. KNOWLES. 41
Role of Neuroendocrine System in Regulation of Mammary Tumors in Different Spe
cies.
J. MEITES .. , ........................................... " ....... , .. . . . . . 47
Evaluation oft he Carcinogenic Effects of Estrogens, Progestins and Oral Contraceptives
on Cervix, Uterus and Ovary of Animals and Man.
V. A. DRILL ............................................................ 59
Assessment of ACTH-Adrenal Activity After Treatment with a Glucocorticoid and an
Antiandrogenic Steroid.
J. GIRARD, J. B. BAUMANN, S. GRAF, G. VAN HEES, M. ROSENTHAL, and K. ZUPPINGER.
With 1 Figure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Neuroendocrine Effects of Neuropsychotropic Drugs and Their Possible Influence on
Toxic Reactions in Animals and Man - The Role of the Dopamine-ProlactiI\ Sys
tem.
R. HOROWSKI and K.-J. GRAF'. With 4 Figures.............................. 93
Motility and Stereotyped Behaviour Induced by Amphetamine and Apomorphine on
Hypophysectomized and on Thyroidectomized Rats.
A. BENAKIS. With 3 Figures .............................................. 105
VI Contents
Induction of Adaptive and Malignant Liver Growth by Drugs
and Environmental Pollutants
Adaptive Liver Growth Induced by Xenobiotic Compounds: Its Nature and Mecha
nism.
R. SCHULTE-HERMANN. With 2 Figures..................................... 113
Growth Control in Regenerating Rat Liver.
K. WEINBREN ........................................................... 125
Control of Liver Growth by Growth Inhibitors (Chalones).
C. NADAL. With 2 Figures................................................ 131
Nucleic Acid and Pyrimidine Nucleotide Metabolism During Liver Growth Induced by
Xenobiotic Compounds (Abstract).
J. SEIFERT and E. BUCHAR ............................................... 143
Early Biological Markers During Liver Carcinogenesis.
P. BANNASCH, H.-J. HACKER, and D. MAYER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Correlation of Liver Growth and Function During Liver Regeneration and Hepatocarci
nogenesis.
H. BARBASON, V. SMOLIAR, and J. VAN CANTFORT. With 7 Figures 157
Liver Growth and Tumorigenesis in Rats.
P. GRASSO. With 10 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Liver Tumors and Steroid Hormones in Rats and Mice.
J. SCHUPPLER and P. GfINZEL. With 5 Figures. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . 181
The Effects of Dieldrin, Diet and Other Environmental Components on Enzyme Func
tion and Tumor Incidence in Livers of CF-l Mice.
H. A. TENNEKES, A. S. WRIGHT, and K. M. DIX ........................... 197
Organotropy as a Toxicological Phenomenon
Enzymes as Regulators of Toxic Reactions by Electrophilic Metabolites.
F. OESCH. With 8 Figures ................................................ 215
Pharmacokinetic Parameters Influencing Tissue Specificity in Chemical Carcinogene
sis.
H.-G. NEUMANN............................ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Organ Specificity of Induction of Activating and Inactivating Enzymes by Cigarette
Smoke and Cigarette Smoke Condensate.
J. E. GIELEN, F. GOUJON, J. SELE, and J. VA N CANTFORT. With 6 Figures. . . . . 239
DNA Repair as Regulatory Factor in the Organotropy of Alkylating Carcino
gens.
P. KLEIHUES, G. DOERJER, J. A. SWENBERG, E. HAUENSTEIN, J. BUCHELER, and H. K.
COOPER. With 4 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
Contents VII
Physiological Mechanisms of Diethylstilbestrol Organotropic Carcinogenesis.
J.-G. FORSBERG......................................................... 263
Diethylstilbestrol Metabolic Transformation in Relation to Organ Specific Tumor. Mani
festation.
M. METZLER and J. A. McLACHLAN. With 3 Figures........................ 275
Organotropic Mutagenesis in Tissues of Chinese Hamsters Induced by Chemical Carci
nogens.
B. J. DEAN, G. HODSON-WALKER, and K. R. SENNER....................... 281
Modulation of the in vivo Covalent Binding of the Carcinogen Benzo(a)pyrene to Rat
Liver DNA by Selective Induction of Microsomal and Nuclear Aryl Hydrocarbon
Hydroxylase Activity.
A. VIVIANI and W. K. LUTZ. With 1 Figure ................................ 285
TCDD - Seveso
Estimation of the TCDD Toxic Potential in the Light of the Seveso Accident.
G. REGGIANI. With 1 Figure.............................................. 291
Free Communications and Poster Sessions
Biological Threshold Limits for Benzene Based on Pharmacokinetics ofInhaled Benzene
in Man.
M. BERLIN, S. HOLM, P. KNUTSSON, and A. TUNEK. With 4 Figures. . . . . . . . . . . 305
Short Term Effects of Clophen A 50 and of Dichlorobiphenyl in Rats.
M. BAUMANN. With 3 Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Toxic Effects of Di-n-octyltin Dichloride on the Thymus in Mice.
G. HENNINGHAUSEN and P. LANGE. With 2 Figures......................... 315
2-Hydroxyoestradiol and (+ )-Cyanidanol-3 Prevent Lipid Peroxidation ofIsolated Rat
Hepatocytes.
H. KAPPUS, D. KOSTER-ALBRECHT, and H. REMMER. With 3 Figures.......... 321
Accentuation of White Phosphorus Induced Fatty Liver by Phenobarbitone in Male
Rats Compared to Female Rats.
A. JACQUESON, M. THEVENIN, J.-M. WARNET, J.-R. CLAUDE, and R. TRUHAUT. 327
Fatty Liver Induced by High Doses of Rifampicin in the Rat: Possible Relation with an
Inhibition of RNA Polymerases in Eukariotic Cells.
A. PIRIOU, J.-M. WARNET, A. JACQUESON, J.-R. CLAUDE, and R. TRUHAUT .... 333
An Experimental Model for the Study of Hepatic Transport and Metabolism of Toxic
Compounds.
M. SCHWENK, V. L6PEZ DEL PINO, and H. REMMER. With 3 Figures.......... 339
VIII Contents
Effects of Subacute Toluene Inhalation on its Metabolism and Disposition in Rat.
E. ELOVAARA, H. SAVOLAINEN, P. PFAFFLI, and H. VAINIO ................... 345
Drug-Nitrite Interactions: Species and Sex Differences in the Formation of Dimethylni
trosamine and its Effects on the Hepatic Enzyme Activities.
Y. OMORI, A. TAKAHASHI, Y. OHNO, H. ISHIWATA, and A. TANIMURA ......... 349
Monoamine Oxidase Inhibiting and Toxic Effects of Acetyl-Phenylhydrazide on Rat
Liver in vivo.
K. QUIRING, V. SCHMIDT, H. CHRISTEN, and L. HAMM. With 2 Figures........ 355
Side Effects of Colloidal Plasmasubstitutes on Hemostasis in Patients with Terminal
Renal Failure.
W. KIRCH, H. KOHLER, and CH. v. GIZYCKI. With 3 Figures................. 359
Accelerated Renal Elimination of Thallium in the Rat Due to Treatment with Furose
mide or Potassium Ions (Abstract).
W. LAMEIJER............................................................ 365
Entrance into Brain of Dextropropoxyphene and the Toxic Metabolite Norpropoxy
phene.
W. L. WAY and J. SCHOU. With 1 Figure .................................. 367
Comparison of the Acute Toxicity of Clioq ui no I, Histamine, and Chloroform in Differ
ent Strains of Mice.
C. PERICIN and P. THOMANN ............................................. 371
Prostaglandins in Rat Placenta Following Acute and Chronic Administration of Mor
phine.
G. M. SCOTO, C. SPADARO, S. SPAMPINATO, N. NOSSAN, R. ARRIGo-REINA, and S.
FERRI. With 4 Figures ................................................... 375
Effects of Two Structurally Different Antispermatogenic Compounds on the Synthesis
of Steroids in Rat Testes.
J. GURTLER and P. DONATSCH. With 2 Figures............................. 381
Ultrastructural Alterations Induced by Two Different Antispermatogenic Agents in the
Seminiferous Epithelium of Rat Testes.
A. HAUSLER and C. HODEL. With 2 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Therapeutic Effects of the Bis-Pyridinium Salts HGG-12, HGG-42 and Atropine,
Benactyzine in Organophosphate Poisoning of Dogs.
W. HAUSER and N. WEGER. With 2 Figures................................ 393
Hormonal Control of Prothrombin Synthesis in Rat Liver Microsomes, with Special
Reference to the Role of Estradiol, Testosterone and Prolactin.
Y. NISHINO. With 2 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
Lifespan Studies on Male and Female Mice and Rats Under SPF-Laboratory Condi
tions.
P. SUTER, H. LUETKEMEIER, N. ZAKOVA, P. CHRISTEN, K. SACHSSE, and R. HESS. With
3 Figures ............................................................... 403
Contents IX
The Loss of Creatine Phosphokinase (CK) from Intramuscular Injection Sites in Rab
bits. A Predictive Tool for Local Toxicity (Abstract).
O. SVENDSEN, F. RASMUSSEN, P. NIELSEN, and E. STEINESS .................. 409
In vivo Covalent Binding of Chemicals to DNA as a Short-Term Test for Carcinogeni
city.
W. K. LUTZ and CH. SCHLATTER.......................................... 411
A Dynamic System for Long-Term Toxicity Studies in Fish Under Laboratory Condi
tions.
R. BATHE. With 3 Figures................................................ 417
Effect ofIntratracheal and Oral Application of Corticosteroids on the Adrenal Function
Test in Beagle Dogs After ACTH-Stimulation.
A. S. BHARGAVA, P. STABEN, F. SmGMUND, CH. SCHOBEL, and P. GiiNZEL. With 6
Figures ................................................................. 425
Drug Actions in Rats with Arteriosclerosis Induced by Toxic Doses of Vita
min Dr
Y. M. BARAKA and H. BEKEMEIER. With 2 Figures.......................... 431
Apparent Tropism of a Vasodilator, Mecinarone, for Melanin-Containing Tissues and
Activation of Melanogenesis in the Beagle (Abstract).
Y. BAILLY and G. RAYNAUD .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437
Estrogenic Partial Effect of Nore thisterone Enanthate in Relation to Tumor Induction in
Rat Mammary Gland.
Y. NISHINO and F. NEUMANN. With 1 Figure............................... 439
The Special Suitability of Inbred Syrian Hamsters for Carcinogenesis Testing.
F. HOMBURGER, R. A. ADAMS, and E. SOTO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Proliferation of Rat Liver Cells in Preneoplastic Nodules After Stimulation of Liver
Growth by Xenobiotic Inducers.
G. OHDE, J. SCHUPPLER, R. SCHULTE-HERMANN, and H. KEIGER. With 3 Fig-
ures . . .. .. . . .. .. . . . .. . . . .. .. .. .. .. . . . . .. . . . . . . .. . . .. .. .. .. . . . . .. . . . . . .. . 451
The Regulative Role of Food Consumption in the Induction of Rat Liver Cell Prolifera
tion by Drugs and Environmental Pollutants.
V. HOFFMANN and R. SCHULTE-HERMANN. With 3 Figures................... 457
Induction of Pre-Malignant Hepatic Lesions: Comparative Effects of Vinyl Chloride and
Trichloroethylene (Abstract).
R. J. LAID, G. STOCKLE, and H. M. BOLT ................•................. 463
Microsomal Vinyl Oxide Synthetase: Modification of its Kinetic Parameters by Chemi
cal Carcinogens.
E. MALVOISIN, M. ROBERFROID, and M. MERCIER. With 3 Figures ............ 465
Influence of Drugs on Activation and Inactivation of Hepatocarcinogenic Nitrosa
mines.
K. E. ApPEL, R. RICKART, M. SCHWARZ, and H. W. KUNZ. With 3 Figures.... 471
x
Contents
Effect of DMN, Phenobarbital and Halothane on the Sedimentation Characteristics of
Rat Liver DNA. '
M. SCHWARZ, K. E. ApPEL, R. RICKART, AND H. W. KUNz. With 1 Figure.... 479
Activities of Polycyclic Hydrocarbon Activating and Inactivating Enzymes in Human
Lungs of Smokers, Non-Smokers, Lung-Cancer and Non-Cancer Patients.
J. LoRENZ, H. SCHMASSMANN, E. OHNHAUS, and F. OESCH .................. 483
Demonstration of Drug-Ethanol Interactions by Changes in Activity of Hepatic Micro
somal Oxidase/Oxygenase Cytochrome P-450 Function.
G. HEINEMEYER, A. G. HILDEBRANDT, I. ROOTS, L. LEHNE, and S. NIGAM. With 3
Figures.. .. . .. .. . . . .. .... . . . . . . . . .. .. . . . . . . . . . . .. .. .. .. .. . .. .. .. . . . .. . .. 491
Alcohol and Aldehyde Dehydrogenase on Chronic Ethanol Intoxication. Effect of
Acetaldehyde and Fat Diet. (Abstract).
M. CASCALES, S. CERDAN, M. R. SANTOS-RUIZ, B. FEIJ60, and A. SANTOS-RUIZ 497
Polycystic Changes in Rat Kidney Induced by Biphenyl Fed in Different Diets.
D. SONDERGAARD and L. BLOM. With 2 Figures ............................ 499
Unscheduled DNA Synthesis in Male Rabbit Germ Cells Induced by Methylmethane
Sulfonate, Cyclophosphamide and Adriamycin.
B. SCHMID and G. ZBINDEN. With 3 Figures................................ 503
Plasma Proteins - Animal Assays on Possible Cardiovascular Side-Effects.
H. RONNEBERGER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
Exploitation of Toxicological Results and its Problems. A Call for Normalisation of
Their Presentation, Apropos of a Pilot Factual Data Bank (Abstract).
J. P. FOURNEAU, M. RAVIART, and R. GERDAY ............................. 515
Computer Analysis and Integration of Animal Pathology Data.
J. M. FACCINI, and D. NAYLOR. With 2 Figures............................ 517
Author Index. . . . . .. .. .. .. .. .. . . . . .. . . . . . .. . . . .. . . . .. .. .. . .. . . . . . . . . .. . . . 521
Subject Index ........................................................... 523
