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AbstractAbstract
[en] The distribution of [14C]-labelled aflatoxin B1 has been studied in mice with the aid of whole-body autoradiography. In addition to the localisation of labelled aflatoxin B1 and/or its metabolites in the liver, bile, kidney, lung and urine an uptake of 14C in the pigment of the Harderian gland and the eye was observed. Uptake of radioactivity was also found in the eyes of the foetuses although their livers did not accumulate radioactivity. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 43 p. 273-279

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AbstractAbstract
[en] In pregnant NMRI mice, low-temperature autoradiography was used to study the distribution of N-14C-nitrosodiethylamine in foetal tissues, and autoradiography with heated tape-sections was used to trace nonvolatile metabolites. Autoradiography with 14C-acetate was used to distinquish the part of the radiography which upon the degradation of N-14C-nitrosodiethylamine may be incorporated in the normal metabolism of the tissues. The results indicated that the non-metabolized N-nitrosodiethylamine passed to the foetuses with an even distribution in most foetal tissues on all the studied days of gestation (day 12, 14, 16 and 18). The autoradiographic results further indicated a metabolism of the substance in the mucosa of the foetal bronchial tree and in the foetal liver on day 18 of gestation, but not in earlier stages of pregnancy. This was substantiated by studies in vitro, which showed a marked capacity of the 18 day old foetal lung and liver (in contrast to tissues from 16 day old foetuses) to form 14CO2 from the N-14C-nitrosodiethylamine. Since the lung and liver are target tissues for the transplacental carcinogenesis of N-nitrosodiethylamine in NMRI mice, a causal relationship between metabolic ability and carcinogenesis may exist in these tissues. (Author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 48 p. 355-363

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AbstractAbstract
[en] The accumulation of radioisotopically labelled lidocaine was investigated in lung slices and perfused lungs of rats. Lidocaine was taken up by rat lung slices incubated in an oxygenated physiological solution (pH 7.4) at 37 deg. 14C-lidocaine accumulated in lung slices to a much greater extent than did 3H-sucrose, and the lidocaine space was approximately 7 times that of the extracellular space. No metabolism of lidocaine took place during the incubation period. The accumulation of lidocaine was inhibited by low temperature, while anaerobic conditions had no inhibitor effect. The uptake of lidocaine (0.028mM) was slightly antagonized by high concentrations of Ca2+ (10 mM). The isolated perfused lung model was used for studying the pulminary absorption of lidocaine from the vascular bed. Lidocaine was rapidly extracted from the perfusion solution and the drug appeared to accumulate in at least two compartments. It seems that in the rat lung a portion of the lidocaine taken up had accumulated within the cells, while some of it may be fixed to the cell surfaces. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 43 p. 156-163

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AbstractAbstract
[en] Hexavalent chromium (Cr-VI), as Na2CrO4 in an aquous solution, was reduced rapidly to the trivalent form (Cr-III) in the presence of glutathione, GSH (0.3-3.0 mM). Such GSH-dependent reduction of Cr-VI can take place in the cytosolic space of Cr-VI-exposed cells, since GSH is found in reactive concentrations in this compartment. The reduction makes chromium essentially impermeable through the cell membrane, explaining the observation that Cr-VI, when added to red cell suspensions, is bound quantitatively intracellularly after a few hours. Diethylmaleate conjugation of the SH-group of the intracellular GSH preventing the oxidation to GSSG, lowered the chromium-uptake significantly, showing that reduced GSH plays a role for the chromium binding. In healthy red cells chromium is partially bound to haemoglobin and partially to small molecular weight substances, probably in the trivalent form. This intracellular chromium cannot be removed to the extracellular space by addition of chelating agents as long as the cell membrane is intact. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 50 p. 310-315

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ANIMALS, BETA DECAY RADIOISOTOPES, BIOLOGICAL MATERIALS, BLOOD, BLOOD CELLS, BODY FLUIDS, CHROMIUM ISOTOPES, ELECTRON CAPTURE RADIOISOTOPES, EVEN-ODD NUCLEI, INTERMEDIATE MASS NUCLEI, ISOTOPES, MAMMALS, NUCLEI, ORGANIC COMPOUNDS, PEPTIDES, POLYPEPTIDES, PRIMATES, PROTEINS, RADIOISOTOPES, VERTEBRATES
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AbstractAbstract
[en] The distribution of 14C-chloramphenicol has been studied in new-born pigs with the aid of whole-body autoradiography. In the lung, liver, adrenal cortex, kidney, myocardium, pancreas, thyroid, spleen and skeletal muscle the amounts of radioactivity were higher than that of the blood short time after injection and remained higher than the blood up to 8 hrs. After 4 and 8 hrs the brain concentration of 14C was also higher than that of the blood. In the bone marrow, however, the concentration did not reach that of the blood during the whole experiment. In the organs more than 90% of the radioactivity was represented by chloramphenicol; the excretory organs, thyroids, and adrenals being exceptions. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 51 p. 345-350

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AbstractAbstract
[en] The distribution of 14C after administration of 14C-DEM was qualitatively similar irrespective of the administration route (intravenous, cutaneous or oral). The major accumulation sites were lacrimal and nasal glands, parotis, liver, and kidney. The main excretion was through the urine and only minor quantities through the faeces and the expired gases. It could be confirmed that the new repellent had a low skin uptake. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 54 p. 41-48

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AbstractAbstract
[en] Rats were treated with lithium added to the diet for five weeks (40 mmol LiCl/kg diet). The mean plasma lithium concentration was 0.48 mmol/l plasma, and the blood was drawn at 8 a.m.. The brains were removed and synaptosomes were prepared according to the method of Gray and Whittaker (1962) and Bradford (1972). The synaptosomes were incubated for 120 min. with 32P-orthophosphate, either in a lithium-containing medium or in a lithium-free medium. The 32P-incorporation was lower in the synaptosomes from lithium-treated rats than the 32P-incorporation in synaptosomes from control rats regardless of the medium chosen. The results indicate that lithium treatment in vivo decreases the 32P-incorporation into synaptosomal phospholipids and that the effect remains after the removal of the lithium ion. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 46 p. 133-137

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ALKALI METALS, ANIMALS, BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, BODY, CENTRAL NERVOUS SYSTEM, DAYS LIVING RADIOISOTOPES, ELEMENTS, ESTERS, ISOTOPES, LIGHT NUCLEI, LIPIDS, MAMMALS, METALS, NERVOUS SYSTEM, NUCLEI, ODD-ODD NUCLEI, ORGANIC COMPOUNDS, ORGANIC PHOSPHORUS COMPOUNDS, ORGANS, OXYGEN COMPOUNDS, PHOSPHORUS COMPOUNDS, PHOSPHORUS ISOTOPES, RADIOISOTOPES, RODENTS, VERTEBRATES
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AbstractAbstract
[en] The distribution and toxicity of cadmium in mice was investigated after single exposure to CdCl2 (labelled with 109Cd) alone or in combination with EDTA (ethylenediaminetetraacetic acid) in Cd: EDTA molar ratios of 1:0.4 or 1:4, respectively, by different routes of exposure: I. Subcutaneous injection, II. Direct infusion into the stomach or the duodenum (under anaesthesia), III. Oral exposure. Most Cd was bound to high molecular weight proteins in liver and kidneys in the Cd-exposed mice (5 hours after exposure) while mice given Cd+EDTA had part of the cadmium also bound to low molecular weight proteins in the livers. No difference in the distribution of Cd among renal proteins were seen between mice from various exposure groups. The complex formation of Cd(II) and EDTA in the present solutions was studied by a potentiometric method. Apart from the formation of a 1:1 Cd-EDTA complex a binuclear Cd2-EDTA complex was formed (accounting for about 35% of the total mol percent distribution of complexes) in the solution where an exess of cadmium with respect to EDTA was present. The results from the present studies show that administration of cadmium in a 2:1-complex with EDTA may lead to an increased toxicity of the metal under certain physiological conditions. The difference in toxicity of cadmium following exposure to the Cd2-EDTA complex by different routes of exposure probably reflects changes in the stability of this complex due to variations in pH and to competition with other metal-binding ligands in vivo. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 46 p. 219-234

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AMINO ACIDS, ANIMALS, BETA DECAY RADIOISOTOPES, CADMIUM ISOTOPES, CARBOXYLIC ACIDS, CHELATING AGENTS, COMPLEXES, ELECTRON CAPTURE RADIOISOTOPES, EVEN-ODD NUCLEI, INTERMEDIATE MASS NUCLEI, ISOTOPES, MAMMALS, NUCLEI, ORGANIC ACIDS, ORGANIC COMPOUNDS, RADIOISOTOPES, RODENTS, VERTEBRATES, YEARS LIVING RADIOISOTOPES
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AbstractAbstract
[en] Several drugs, mainly polycyclic amines, are accumulated in melanin-containing tissues. They are bound to preformed melanin (both in vivo and in vitro). Thiouracil is accumulated into melanin according to another principle: It is incorporated as a false precurser during melanin formation. It is thus taken up only in growing melanin, e.g. in the eye of pigmented mouse foetuses or in melanomas. The acceptance of a foreign substance during the formation of a foetal tissue seems theoretically important. We are also interested in the practical viewpoint of using false melanin precursors as selective melanoma seekers. Some related substances are therefore compared with respect to incorporation into growing melanin. The thiouracil uptake in the ocular melanin of a 5 day old mouse was 276 times higher than that of a 3 month old mouse based on weight units of melanin. Thiourea is incorporated in growing melanin as well but also binds slightly to preformed melanin. Uracil and fluorouracil showed no specific uptake into growing melanin. It thus seems as if the sulfur is essential for the incorporation into the melanin polymer. 35S-thiouracil and 2-thio(2-14C)uracil showed the same high uptake, indicating that at least part of the uracil moiety is incorporated together with the sulfur. There seems to be a relation between the property to be incorporated into melanin and the thyrostatic activity. Both in the formation of melanin and thyroid hormones, tyrosine is the physiological precursor and both reactions are catalyzed by oxidizing enzymes. Properly labelled thiouracil derivatives seem to be promising melanoma seekers for diagnostic and radiotherapeutic purposes. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 49 p. 141-149

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ANIMALS, ANTITHYROID DRUGS, AZINES, BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, CARBON COMPOUNDS, DAYS LIVING RADIOISOTOPES, DISEASES, DRUGS, EVEN-ODD NUCLEI, HETEROCYCLIC COMPOUNDS, HYDROXY COMPOUNDS, ISOTOPES, LIGHT NUCLEI, MAMMALS, NEOPLASMS, NUCLEI, ORGANIC COMPOUNDS, ORGANIC NITROGEN COMPOUNDS, ORGANIC SULFUR COMPOUNDS, PIGMENTS, PYRIMIDINES, RADIOISOTOPES, RODENTS, SULFUR ISOTOPES, THIOLS, URACILS, VERTEBRATES
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AbstractAbstract
[en] Fractionation of the bile from rats injected with 65ZnCL2(5 μmol/kg) showed that zinc was mainly bound to low molecular weight compounds eluted corresponding to the zinc-glutathione complexes. Diethylmaleate (3.9 mmol/kg), cyclohexene oxide (4.9 mmol/kg) and acrylamide (3.5 mmol/kg) administered intraperitoneally to rats caused a rapid decrease in the endogenous excretion of both zinc and reduced glutathione into bile. This depression probably reflects the conjugation of the aforementioned substances to glutathione in the liver cells. These results indicate that zinc is transferred from liver to bile by glutathione dependent process and most likely as zinc-glutathione complexes. (author)
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Acta Pharmacologica et Toxicologica; ISSN 0001-6683;
; v. 49 p. 190-194

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ANIMALS, BETA DECAY RADIOISOTOPES, BETA-PLUS DECAY RADIOISOTOPES, BIOLOGICAL MATERIALS, BODY FLUIDS, CHLORIDES, CHLORINE COMPOUNDS, CLEARANCE, DAYS LIVING RADIOISOTOPES, ELECTRON CAPTURE RADIOISOTOPES, EVEN-ODD NUCLEI, HALIDES, HALOGEN COMPOUNDS, INTERMEDIATE MASS NUCLEI, ISOTOPES, MAMMALS, NUCLEI, ORGANIC COMPOUNDS, PEPTIDES, POLYPEPTIDES, PROTEINS, RADIOISOTOPES, RODENTS, VERTEBRATES, ZINC COMPOUNDS, ZINC ISOTOPES
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