J.L. Kaw

Some biochemical and histopathological changes induced by polyvinyl chloride dust in rat lung

Abstract Enzymatic and pathomorphologic alterations in rat lungs were studied at different time intervals up to 180 days after a single intratracheal administration of 25 mg of polyvinyl chloride dust. The activities of two energy-linked enzymes, succinic dehydrogenase (SDH) and adenosine triphosphatase (ATPase), and three lysosomal enzymes, acid phosphatase, β-glucuronidase, and ribonuclease, were significantly increased in the early period and then started to decline. The activities of SDH and ATPase reached control values at 150 days, while those of the lysosomal enzymes remained significantly higher up to this period. Histopathologically, the pulmonary response was in the form of acute inflammatory changes during the early stages of dust burden, followed by the development of granulomatous lesions containing small amounts of stromal elements.

Lactate dehydrogenase isoenzymes in macrophages and serum during the development of pulmonary silicosis in the rat

The lactate dehydrogenase (LDH) isoenzyme pattern in macrophages (peritoneal and alveolar) in the rat was studied on polyacrylamide gel electrophoresis. Further, the release of LDH isoenzymes from cultured macrophages exposed to silica dust and also the pattern of serum LDH isoenzymes in silica exposed animals were investigated. The isoenzyme pattern of the alveolar macrophages showed all the five bands, contrary to peritoneal macrophages in which two bands, viz. LDH1 and LDH2, were missing. Silica-exposed macrophages liberated LDH5 in the supernatant culture medium. This LDH isoenzyme also increased in the serum of silicotic rats during the early stages of the development of the disease.

Effect of ascorbic acid on pulmonary silicosis of guinea pigs.

The role of ascorbic acid on developing pulmonary silicosis of normal and scorbutic guinea pigs was studied for 115 days. In normal silicotic guinea pigs an increasing concentration of ascorbic acid in lungs with the advancement of silicosis was observed. The increase of ascorbic acid was directly related to collagen percentage. Adrenal ascorbic acid showed an increase with lapse of time, and blood ascorbic acid did not show any alteration. In scorbutic silicotic guinea pigs the collagen fiber formation was retarded but the hydroxyproline contents and acid mucopolysaccharide remained the same as in normal silicotics.

Low dose effects of fibrous and non-fibrous mineral dusts on the proliferation of mammalian cells in vitro

This report presents preliminary results of studies on the growth stimulating properties of mineral dusts. The studies were carried out with Syrian hamster diploid embryonic fibroblasts and Chinese hamster fibroblasts, line B14F28. Toxicity testing was done by the determination of the plating efficiency as a measure of growth and viability. The following dusts were used: the modified UICC asbestos fibres amosite, (AFF) crocidolite (KFF), chrysotile (KFF): in addition glass fibre (GFF), corundum and quartz DQ12. Concentrations > 2 microg/cm2 of AFF, CFF, KFF and GFF depressed the plating efficiency of B14F28 cells in a dose-dependent manner, but all of the fibres and corundum increased colony sizes at concentrations of 0.16-0.33 microg/cm2, in the case of corundum, AFF, KFF, and CFF also at up to 0.66 or 1.32 microg/cm2. DQ12 did not enhance colony growth. The stimulation of proliferation could be demonstrated both in terms of colony size (diameter) and cell numbers. The factor(s) responsible for proliferation stimulation reside in the supernatant, since the medium of dust-treated cell cultures was able to stimulate colony growth after removal of the dusts by filtration. The results indicate the induction of growth factors (cytokines) by low concentrations of the mineral dusts. Experiments concerning the effect of dusts on embryonic golden hamster fibroblasts yielded similar results. The plating efficiency was inhibited by concentrations of GFF and CFF > 0.25 microg cm2 and by AFF, KFF, GFF and corundum at concentrations > 5 microg/cm2, but colony counts were significantly increased by AFF, KFF and corundum at concentrations of 0.25-3 microg/cm2. This biological reaction which was observed in different cell types appears to be especially relevant in the context of environmental exposure where low dust concentrations prevail.

Alterations in the pulmonary and systemic immune response in rats exposed to coal fly ash.

The effect of intratracheally injected fly ash on the development of pulmonary and systemic immunity was studied in rats. Following intratracheal and intraperitoneal immunisation with sheep red blood cells (SRBC) there was an appearance of antibody forming cells (AFC) in lung associated lymph nodes (LALN) of animals exposed to either fly ash or physiological saline. Enumeration of AFC in LALN after immunisation by either of the routes, revealed a reduction in the number of AFC in LALN of fly ash exposed rats in comparison to saline exposed animals. The reduction in the number of AFC was more pronounced after exposure of Cd-coated fly ash. The AFC appeared in the spleen only after immunisation through intraperitoneal route and the number of AFC in spleen of the fly ash and saline exposed group of animals did not show any significant difference. These results demonstrate that fly ash burden of lungs results in an impairment of the local immune response of the lungs without an associated effect on the systemic immunity.

Ranking toxicity of industrial dusts by bronchoalveolar lavage fluid analysis

Female wistar rats were inoculated intratracheally with 10 mg/ml suspensions of various dusts, viz: quartz, fly ash, mica and corundum in physiological saline. Biochemical markers of bronchoalveolar lavage fluid (BALF) were analysed 8 days after the instillation of the dusts. Elevated levels of proteins, sialic acid and phospholipid contents and the activity of lactate dehydrogenase correlated well with the degree of the known fibrogenic potential of different dusts in the lungs in the following order, quartz greater than fly ash greater than mica greater than corundum. beta-glucuronidase activity, was however, only elevated in the quartz inoculated group of rats. It is suggested that biochemical constituents of BALF analysed shortly after the exposure to different dusts can be useful to mirror alterations in the tissue response to mineral dusts.

Amino acid changes and pulmonary response of rats to silica dust

Abstract The effect of intratracheal injection of quartz on the free amino acids of lung, serum, and liver and the bound amino acids of lung was studied in rats, at intervals preceding and following the formation of collagen. The studies revealed that amino acid metabolism is significantly altered in silicotic rat lung. Changes in the body pool of amino acids seem to be related to both collagen and noncollagen formation in silicotic lung. It appears that some of the amino acid residues for collagen formation in lung in response to silica exposure are made available by the in situ formation from available precursors, while others are contributed by other organs, especially liver. A central role for glutamic acid metabolism in the genesis of pulmonary fibrosis is discussed.

Modification of pulmonary silicotic reaction in rats exposed to coal fly ash

Quartz exposure resulted in an increase in the wet weight, dry weight and collagen contents of lungs. Animals inoculated comparable amounts of fly ash revealed a statistically insignificant increase in these parameters. In silicotic rats exposed to fly ash the increase in the wet weight, dry weight and collagen contents of lungs was reduced in comparison to silicotic animals unexposed to coal fly ash. Histological examination of lungs revealed the development of silicotic granulomata with reticulin and collagen fibre formation. The difference in the development of these lesions was less pronounced when a blindfold comparison was made between the silicotic animals, exposed or unexposed to coal fly ash. The increased activity of LDH in the bronchoalveolar lavage (BAL) of rats exposed to quartz alone was mitigated significantly in silicotic animals subsequently exposed to coal fly ash. The protein content of the BAL increased significantly more in quartz-fly ash exposed animals than in rats exposed to either dust alone. The total cellular elements of the BAL were increased in rats exposed to quartz alone (p less than 0.005). The results demonstrate that fly ash exposure can significantly modify the development of a silicotic pulmonary reaction.

Early response of gastric mucosa to ingested asbestos dust and the dissolution of nickel

The gastric response evoked by asbestos fibers (chrysotile, tremolite, anthophyllite, and amosite) was studied in guinea pigs 6 hours after oral administration. Substantial amounts of nickel were leached from the dusts into the gastric juice, the maximum being with chrysotile. Histopathological examination of stomach and biochemical analysis for total acidity, peptic activity, and the contents of mucin did not reveal any alterations of significance.

Antibody forming cell response to nickel and nickel-coated fly ash in rats

The potential of nickel as nickel chloride, native fly ash and Ni-coated fly ash to alter pulmonary and systemic immune response was evaluated upon intratracheal (I/T) exposure of rats. The animals were sensitised with sheep red blood cells (SRBC) through I/T and intraperitoneal (I/P) routes. Nickel exposure resulted in a decrease in the number of antibody forming cells (AFC) in lung associated lymph nodes (LALN) and spleen. In rats exposed to native fly ash there was a reduction in the number of AFC in LALN but not in spleen. The results did not demonstrate any significant difference in the immunosuppression of fly ash and Ni-coated fly ash exposed rats. The decrease in AFC formation in Ni-coated fly ash exposed animals was of a lesser magnitude than in rats exposed to Ni-alone.