[en] In a strain of ducks sensitive to the eggshell-thinning effect of p-p'-DDE, administration of 40 mg/kg of the compound in the food for 45 days reduced the eggshell index (EI) by 13% and the content of calcium in the fluid of the shell gland forming an eggshell by 36%, and raised the calcium content of the shell gland mucosa by 19%, compared with the control values. DDE inhibited the translocation (secretion) of calcium between the gland mucosa and the uterine cavity. The ATP-dependent binding of Ca²⁺ to the subcellular fractions of the gland mucosa was reduced in DDE-treated ducks. The Ca²⁺ binding to a microsomal subfraction (FI) rich in fragments of the plasma membrane was reduced by 16%, whereas that to a subfraction FIII which bound Ca²⁺ at a very high rate was reduced by 36%. The latter may contain calcium-secreting granules of the gland. In the mitochondrial fraction the Ca²⁺ binding was reduced by 35%. In the domestic fowl DDE did not lower EI or interfered with the translocation of calcium between the shell gland mucosa and uterine cavity. DDE administration increased the Ca²⁺ binding to FI by 26%, the binding to other subfractions was not changed significantly. DDE may interfere with the stimulus-secretion mechanism of the eggshell gland in ducks through its effect on Ca²⁺ binding. (author)

[en] Melanotic melanomas show a high rate of melanin synthesis. Foreign substances that are accepted as precursors in the formation of melanin may therefore be useful in the diagnosis and therapy of malignant melanotic melanomas, if labelled with suitable radionuclides. We have earlier reported that 2-thiouracil is incorporated in melanotic melanomas, apparently as a false melanin precursor. In the present study it is shown that methimazole and 5-iodo-2-thiouracil are as well accepted as melanin precursors. 5-Iodo-2-thiouracil is of sp ecial interest, since iodine has many clinically useful radioisotopes. The chemical properties that characterize substances which are incorporated as false precursors into melanin are discussed. A free sulfur ligand of the thioamides (2-thiouracil, 5-iodo-2-thiouracil, methimazole and thiourea are all incorporated into melanin) seems to be essential and the link between these substances and the melanin. Uracil (which lacks sulfur) and 2-benzylthiouracil (where the sulfur is blocked with a benzyl group) do not attach to melanin. Our coclusion therefore is that the thioureylene strucrture is the smallest common molecular fragment of the false melanin precursors. (author)

[en] Uptake of mercury by brain after intravenous injection of elemental mercury was investigated in the rat. Catalase activity was inhibited by aminotriazole either by intraperitoneal affecting catalase in most tissues of the animal or by intraventricular injections affecting catalase in the brain selectively. Uptake of elemental mercury by rat brain was not influenced by intraperitoneal administration of aminotriazole resulting in 50% inhibition of brain catalase. However, when the inhibitor was injected intraventricularly in concentrations to give a 50% inhibition of brain catalase, it was shown that the mercury uptake by brain was significantly decreased. In the latter case when only brain catalase was inhibited and the supply of elemtal mercury to brain was maintained, mercury uptake by brain was proportional to the activity of catalase in brain tissue and to the injected amount of elemental mercury. Contrary to the intraventricular injection of aminotriazole, in animals recieving aminotriazole intraperitoneally prior to elemental mercury injection, we suggest that the lower activity of brain catalse is compensated by an increased supply of elemtal mercury caused by the generally lower oxidation rate in the animal. This view is supported by the finding that mercury uptake by liver increased due to aminotriazole intraperitoneally although activity of catalase was depressed. (author)

[en] The distribution of ⁷⁴As-labelled and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the ⁷⁴As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in material tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution pucture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10μM) while arsenate seemed to be without effect at concentrations up to 200 μM (highest tested). Arsenate, however, showed a potential of the arsenite toxicity. (author)

[en] The tissue distribution of 4-¹⁴C-lynestrenol (17 α-ethynyl-oestr-4-en-17β-ol) following oral administration to pregnant rats was studied by whole body autoradiography and liquid scintillation counting. Pregnant females were sacrificed on days 10, 12, 14 and 19 of gestation, in each case 5 hours after oral administration of 43 μCi 4-¹⁴C-lynestrenol per animal. The isotopelabelled compound was distributed throughout most tissues, including the fetuses. The highest concentrations were found in the liver, while there was lower activity in the fatty tissues and the activity in fetuses was comparable with that in the brain. The placental transfer was verified by the results of liquid scintillation counting. The concentration of labelled substance in the fetuses increased with the duration of pregnancy. (author)

[en] One of the main ecotoxicological effects of DDT and its stable metabolite DDE is to reduce the reproductive succes in several species of birds by decreasing the thickness of the eggshell. In two different strains of ducks (Anas platyrhynchos var.) addition of 40 mg/kg dry weight of p-p-DDE to the diet for 45 days produced a significant and long-lasting reduction of the shell thickness, measured as eggshell index. The reduction was more marked in Indian Runner Ducks (IRD; 30+-3%) than in a SwedishxRouen breed SR; 10+-2%. The p-p-DDE residues in the egg yolk + egg white were almost similar in the two strains; 38+-2 and 51+-6 p.p.m. (wet weitht) respectively. In the IRD 40 mg/kg of o-p-DDE in the diet for 45 days was much less potent in reducing the eggshell index (8+-3%) than the p-p isomer; the amount of residue of the o-p isomer in the eggs (2.2+-0.1 p.p.m.) was also smaller. A homogenate of the shell gland from the SR breed accumulated ⁴⁵Ca²⁺ in the presence of ATP. The accumulation was inhibited about 50% by 5 mM sodium azide and 100% by 3 mM mersalyl- p.p- and o-p-DDE in the incubation medium both reduced the Ca²⁺binding, in a similar and dosedependent manner. The threshold concentration was about 20 p.p.m.; 40 p.p.m. reduced the accumulation by about 40%. DDE may reduce eggshell thickness by inhibiting the Ca binding to the membranes of the cells of the eggshell gland. (author)

[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)

[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)

[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)

[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)