Pathways and quantification of insoluble particles in the lung compartments of the rat.

The aim of this investigation was focused on mechanisms involved in toxicokinetics of particles and fibers within the rat lung. Biologically inert polystyrene particles or an asbestos--particle comixture were followed in their pathways of deposition and retention in the lung, particularly in the alveolar space and their accumulation in the lymph node tissue of exposed rats. One group of Wistar rats was intratracheally instilled with 0.4 ml phosphate buffered saline containing 2.4 x 10(8) inert polystyrene microspheres, a second group of animals was instilled with comixture containing 1.25 mg/ml of crocidolit asbestos fibers and previously prepared microspheres. Bronchoalveolar lavage of each lung was performed on post-instillation days 1, 7, 30, 80 and 150. Particles associated with alveolar phagocytes were counted using light microscopy. The lung and lymph node tissues were chemically dissolved and tissue aliquots passed through Nucleopor membrane filters. The number of particles in the tissue aliquot samples was determined using fluorescence microscopy. The results show that the fate of particulates in the respiratory system is highly dependent on the physical properties of the instilled material. Clearance patterns for particles and fibers are markedly different. Long-term consequences are the translocation and retention of fibrous material in the interstitum, involving the major route of clearance through the lymphatics.

The role of intratracheal instillation and bronchoalveolar lavage in the investigation of mechanisms underlying lung disorders--an animal model.

When studying the course and etiopathological mechanisms underlying human lung disorders caused by external factors, it is extremely important to extend the investigations by using an experimental animal model. The advantage of such a model, in respect to well-known ethical limits involved in a human study. Is that one can precisely design the experiment, keep the relevant parameters under strict control and limtate the pathological conditions to be studied. Bronchoalveolar lavage Is a useful toxicological modality for gaining access to the constituents of the lower respiratory tract. Analyses of both soluble and Insoluble contents of the bronchoalveolar lavage fluid are now increasingly being used to monitor the course of lung disorders. The use of an appropriate animal Instillation model provides an insight into the kinetics of the substance in between free lung cells and lung compartments. The bronchoalveolar lavage assay following intratracheal instillation of an experimental animal has proven to be a useful and fast technique for the detection of lung injury caused by toxicants.

The rate of DNA synthesis in HeLa cells during combined long-term and acute exposures to lead.

Asynchronous populations of HeLa cells growing as monolayers were incubated in a nutritive medium supplemented with a low concentration of 10(-5) M lead chloride for several months. At various time intervals the [3H]thymidine uptake was measured in the DNA of the cells by a scintillation counting technique. During the first 2 weeks of incubation, the rate of DNA synthesis was slightly reduced. After 3 weeks the synthesis returned to normal and later it was a little enhanced. The pretreated cells tolerated acute intoxication by a high lead concentration of 2.5 x 10(-4) M without a change in the rate of DNA synthesis. The cells also proliferated 1 year in a culture medium supplemented with a progressively increasing lead concentration. However, the survival of cells at the highest lead concentration lasted only a few days. After return to a metal-free medium the cells again became very sensitive to lead as shown by the reduced rate of DNA synthesis. The transitory character of adaptation indicates that there was no direct genetic involvement.

[Lead and cadmium toxicity in established mammalian cell lines]. / Toxicité du plomb et du cadmium pour des lignées continues de cellules de Mammifères.

Lead and cadmium toxicity was evaluated in three mammalian cell lines (tumour : HeLa, transformed : XC and normal : NRK) by means of the modifications of the 3H-TdR incorporation rate in the nucleus of the treated cells. The three cell lines showed different degrees of sensitivity. Sensitivity depended on the line, metal, its concentration and duration of incubation. Cadmium was found to be at least five times more toxic than lead except at low concentration. The normal cell line was more sensitive to cadmium and less sensitive to lead than other lines.