Influence of heavy metals upon the retention and mobilization of polonium-210 in rats.

PURPOSE: To provide information about the tissue retention and mobilization of the alpha-emitting radionuclide, polonium-210 (210Po), in rats under combined exposure to heavy metal ions and the chelating agent, 2, 3-dimercaptopropane-1-sulfonate (DMPS). MATERIALS AND METHODS: Rats were pre-exposed intraperitoneally to either CdCl2 or Pb(CH3COO)2. 9 or 15 h later they received 210Po nitrate intravenously. The retention and excretion of 210Po via the urine and faeces of pre-exposed rats, as well as in pre-exposed rats treated with DMPS, were followed. The radioactivity due to 210Po in a broad spectrum of body tissues and excreta was measured by the liquid scintillation counting after sample digestion in a mixture of perchloric acid and hydrogen peroxide. The immunohistochemical localization of metallothioneins (MT) was studied using a mixture of murine monoclonal antibodies directed against MT I+II. RESULTS: The present study revealed different tissue distributions of polonium-210 in the rats pre-exposed to lead or cadmium ions when compared with that in 210Po only controls. Under combined exposure to Pb or Cd, the spontaneous excretion of 210Po was enhanced and could be further enhanced by treatment with DMPS. Treatment with this chelator was efficient even when its start was postponed until 24h after internal contamination of the body with 210Po. CONCLUSIONS: Polonium-210 is bound in vivo to binding sites on various biomolecules, among them erythrocytic enzymes and MT. This phenomenon explains the different affinity and overall distribution of 210Po in control body tissues. When the appropriate binding sites are occupied by lead or cadmium, enhanced natural excretion of polonium-210 occurs.

Reduction of subacute lethal radiotoxicity of polonium-210 in rats by chelating agents.

The protective effect of N,N'-di(2-hydroxyethyl)ethylene-diamine-N,N'-biscarbodithioate (HOEtTTC) against the subacute lethal radiotoxicity of polonium-210 was investigated in a survival study and by histopathological and haematological examinations of some organs and tissues in Sprague-Dawley rats. This effect was compared with that of N,N'-diethylamine-N-carbodithioate (diethy dithiocarbamate, DDTC). In the survival study, rats injected in intravenously solely with a lethal amount of 210Po (1.45 MBq kg-1 body mass) died within 14-44 days while 90% of rats treated with HOEtTTC survived for 5 months until sacrificed. When treated with DDTC all rats died within 36-93 days. In the histopathological examination, relevant changes resulting from incorporation of 210Po were found in lymph nodes, thymus and humeral bone marrow. After the treatment with HOEtTTC no pathological changes were observed. In the haematological examination, severe reduction in blood and femoral bone marrow (BM) cell counts was revealed in rats injected with 210Po. This reduction was reversed by treatment with HOEtTTC. Treatment with DDTC led only to partial recovery of blood and BM cell count. In conclusion, under the conditions of the experiment only HOEtTTC was fully effective in reducing subacute lethal radiotoxicity of 210Po.

Effects of magnetic field exposure on the development of lung fibrosis elicited by industrial pollutants.

Lung injury elicited by a single intratracheal instillation of fibrogenic (quartz) and nuisance (anatase) dusts and/or weekly repeated instillation of CdCl2 solution combined with sinusoidal (50 Hz, 10 mT) magnetic field (MF) exposure was studied in male rats. Combined effects in bronchoalveolar lavage (BAL), rat lungs and regional lymph nodes after 4 months of MF exposure (1 h/5 days per week) were evaluated biochemically and by cytological and histopathological examination. Damage of cell membranes in the cell part of BAL due to MF exposure was not observed in the examined animal groups. Following MF exposure, decreased synthesis of collagen proteins (incorporation of [14C]proline) was demonstrated in lungs with quartz dust burden. Histological examination revealed differences in the lung tissue reaction suggesting the modification of the repair process due to MF exposure following experimental injury in both quartz and cadmium groups.

[Serum lysozyme and copper levels in rats after the administration of dust]. / Obsah lyzozýmu a medi v sérech potkanu po podání prachu.

Changes in the content of lysozyme and copper were studied in the blood serum of rats in four time intervals (1, 2, 12, and 24 weeks) after administration of 50 mg TiO2, Sio2 or coal dust and the copper content was also studied 12 weeks after administration of 3 industrial dusts. The obtained results were supplemented by histopathological examinations and in the 12-week interval by the determination of the lung wet weight. The lysozyme content was statistically significantly increased compared to controls practically over the whole time course with differences in the level of the response to SiO2 in comparison with the response to TiO2 and coal. With the exception of the first interval, the serum copper level was statistically significantly increased only after quartz dust administration. The obtained results were compared with literary data and findings reported from clinical practice.

The use of the DENTACRYL rapid (Spofa) resin for preparation of the rat tracheobronchial casts.

We have made tracheobronchial casts of the rat lungs using DENTACRYL Rapid (Spofa)--the synthetic methacrylic resin of Czechoslovak origin. The details of the method are fully described. The differences between preparations of the intact rat tracheobronchial trees and those of the rats after quartz instillation are illustrated. These differences are analogous to the commonly described changes in bronchograms.

Acrylonitrile potentiation of oxygen toxicity in rats.

Single intraperitoneal injection of acrylonitrile, administered prior to the start, at the onset, or during oxygen exposure, respectively, in all cases significantly impaired the survival rate of rats exposed to 98% oxygen. Short periods of lung glutathione depletion by acrylonitrile accelerated the manifestation of O2 toxicity regardless of their timing with respect to the start of oxygen exposure, but in dependence on their intensity and duration. However, the effect of acrylonitrile was probably not solely glutathione-depletion-mediated, since O2 toxicity was enhanced even by acrylonitrile injection, given sufficiently in advance to allow the lung glutathione level to recover before the oxygen exposure started.

Calcification of poly(2-hydroxyethyl methacrylate)-collagen composites implanted in rats.

Samples of the polyHEMA-collagen composites with varying collagen content have been implanted into the popliteal region of rats. Three, six and twelve months after the implantation, calcification of the implanted material was determined using a radioactive indicator. At the same time, the implants and surrounding tissue were examined histologically. The degree of calcification of the implants was dependent on the collagen content; it was more pronounced with a higher amount of collagen. The composites with 30% (w/w) or more collagen were biodegraded during the long-term implantation. It is suggested that the composites containing less than 20% (w/w) of fibrillar collagen are used for biomedical applications and that those with a higher collagen content for the in vitro studies.

Changes in pulmonary connective tissue proteins after a single intratracheal instillation of cadmium chloride in the rat.

Changes of soluble and insoluble fractions of pulmonary connective tissue proteins were studied in rats for 2-84 days following a single intratracheal instillation of cadmium chloride (10 micrograms Cd2+/lung). A transient decrease in body weight and an immediate increase in lung wet weight (200% of control value, P less than 0.01) were observed. Incorporation of [14C]proline and its conversion to [14C]hydroxyproline in vivo into different soluble and insoluble fractions of connective tissue revealed an increased metabolic turnover elicited by cadmium intoxication. A lag in the maturation of collagen into higher functional forms in the early phase of the process was demonstrated. A striking decrease in elastin was found in first 7 days (40-50%). However, this acute damage of pulmonary connective tissue was followed by a permanent increase of collagen and elastin concentration in the later phase of recovery. Histopathologic examination 14-84 days after cadmium instillation confirmed the presence of lesions in pulmonary tissue with an initial inflammation followed by reparatory changes.

Biomonitoring of environmental pollution hazards from a nickel smelter waste dump.

Longterm field exposure study was carried out on 10 rabbits placed for 6 months in a bioindication station located about 3 km downwind of a disposal site of nickel smelter waste dump. As revealed by the method of atomic absorption spectrophotometry, all of these animals showed elevated nickel and chromium levels in their body organs and hair. These findings were paralleled by histologic abnormalities in the lungs and liver tissues. Average dustfall values at the site of exposure did not exceed 5.5 g X m-2 X 30 d-1 during the period of observation. Dustfall deposits in this location contained nickel and chromium in amounts that were higher than in control locality. Analogous experiments on Wistar rats were carried out in a laboratory exposure chamber (exposure 4 h/day, 5 days/week, for a period of 6 months). After exposures to 50 mg X m-3 of metallic dust, lung parenchyma of rats was characterized by the presence of dust particles in various phases of phagocytosis as well as the presence of badly damaged or disintegrated alveolar macrophage cells, which pointed to metallic aerosol toxicity for biomembranes. The technique of air pollution biomonitoring on animals, correlated with the data on ambient air concentrations of the suspended particulate matter and its content of trace metals, appears to be a well suitable tool in establishing the potential air pollution hazards to the exposed populations living in the area of concern.

Acrylonitrile inhalation in rats: I. Effect on intermediary metabolism.

In male Wistar rats the inhalation exposure to acrylonitrile (AN), 280 mg X m-3, 8 hours a day for five days significantly decreased the serum concentration of cholesterol and triglycerides, but the liver concentrations of phospholipids, and esterified fatty acids were unchanged. The liver microsomal protein and cytochrome P-450 content decreased significantly. On the other hand the levels of glucose, lactate and pyruvate in the blood and brain significantly increased up to 250% of controls. A microscopic examination of the lungs, liver, kidneys and adrenals did not show structural changes and the numbers and enzyme activities of alveolar macrophages were also unaffected. In single 12-hour inhalation exposures the elevation of blood glucose was proportional to the inhaled concentration of AN (average concentrations 57, 125, or 271 mg X m-3); the effect was significant at the lowest AN concentration and was intensified in the glucose tolerance test. The elevation of blood glucose proved to be the most sensitive and dose-related indicator of AN exposure of those observed.

Thy-1 epitopes are expressed on murine myeloid leukemia and reticulum sarcoma cells.

Expression of Thy-1.2 specificities in cells from 29 primary spontaneous leukemias of random-bred ICR Swiss mice was examined by cell membrane and cytoplasmic immunofluorescence with monoclonal HO-13-4 antibody [1]. The Thy-1.2 epitopes were detected in all thymic lymphomas and were absent in the lymphomas of non-thymic origin. Unexpectedly, the Thy-1.2 epitopes were also detected in 71% (5/7) of myeloid leukemias and 40% (4/10) of reticulum cell sarcomas examined.

Changes in pulmonary connective tissue after a single intratracheal instillation of papain in the rat.

The effect of a single intratracheal instillation of 2 mg of papain on metabolic changes of collagen and elastin in lungs was studied in rats labeled with [14C]proline in vivo. The total amount, concentration, specific and total radioactivity of both proteins were examined during the 28 days after papain administration. In the early period (1 to 3 days) a loss of elastin content (about 50% of control; p less than 0.01) was found, whereas collagen content increased (p less than 0.05). Simultaneously, the specific as well as the total radioactivity of both proteins was enhanced (p less than 0.01) which indicated an accelerated biosynthesis and metabolic turnover. This fact was reflected in the increased amounts of both collagen and elastin in the lungs 14 and 28 days after instillation of the enzyme. The changes in connective tissue proteins accompanied a large increase in lung weight (200% that of the control rats; p less than 0.01) immediately after the exposure. Toward the end of the 28-day period, the increase was smaller. The enzymatic damage probably induced the formation of nonfunctional elastin and fibrous scars as a consequence of the healing process.

Role of time and concentration on carbon tetrachloride toxicity in rats.

The hepatotoxic effect of different exposure schemes to carbon tetrachloride (CCl4) was studied in inhalation experiments in rats. The duration of exposures at different concentrations of CCl4 vapours in air was changed in such a way as to give a constant product of concentration and time (CT). The animals were exposed for 4 successive days a week. A concentration of 1,625 mg/m3 (250 ppm) CCl4 for 72 min (CT = 300 ppm x h) caused a higher increase in SGPT activity than the exposure to 325 mg/m3 (50 ppm) for 6 h (CT = 300); the effect of 6,500 mg/m3 (1,000 ppm) for 3 min six times at 1-h intervals (CT = 300) had a much smaller effect than the exposure to 6,500 mg/m3 (1,000 ppm) for 18 min (again CT = 300) (1 ppm CCl4 = 6.5 mg/m3). Similar results were obtained at other concentrations and by increasing the number of exposures up to 18; the effects were also confirmed by other biochemical changes in blood serum and liver and by histological examination of the liver. The results indicate that the severity of liver lesions is more influenced by the concentration of CCl4 in the inhaled air (and accordingly in the blood entering the liver) than by the total inhaled (and absorbed) amount of CCl4. This also explains the differences between the two types of exposure in the concentration of 6,500 mg/m3 (1,000 ppm): blood cannot be saturated with CCl4 to the same level within 3 min as within 18 min of exposure.

Cell-surface adhesiveness of mouse leukemias.

Cell-surface adhesiveness of forty-one primary mouse leukemias was quantitatively examined by the Latex (polystyrene) particle adherence (LPA) assay. Mean surface adhesiveness of leukemic cell populations was found to be substantially lower than that of normal mouse thymus, lymph node and spleen cell populations. No significant differences were found among mean LPA-positivity of sixteen thymic lymphomas, sixteen reticulum cell sarcomas and six myelogenous leukemias examined; the LPA-positivity of two nonthymic lymphomas and one undifferentiated leukemia was higher and comparable with that of normal mouse thymus cells. Comparison of the LPA-positivity of normal thymus cells and thymic lymphomas indicated that the malignant conversion of thymus cells was either accompanied or followed by a decreased cell-surface adhesiveness.