British Journal of Experimental Pathology

Our medical research library holds 42 studies published in British Journal of Experimental Pathology (1963–1988). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 38 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 4 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Blackwell
• Published: 1920–1989, England
• Language: English
• ISSN: 0007-1021 (print)
• Continued by: Journal of Experimental Pathology (Oxford, England)
• Its record in the NLM Catalog

1980s

• Comparisons of the pathogenicity of long and short fibres of chrysotile asbestos in rats. J.M. Davis, A.D. Jones. 1988;69(5):717-37. PubMed · Free full text

  Abstract

  Long-term inhalation and intraperitoneal injection studies were undertaken with laboratory rats treated with a specially prepared short-fibre sample of Canadian chrysotile asbestos. This was compared, at an equal mass dose, to dust generated from the same chrysotile batch so as to contain the highest possible number of long fibres. The long-fibre cloud contained roughly five times more fibres greater than 5 micron in length as seen by phase contrast optical microscopy (PCOM). For increasing lengths, the ratio between the dust clouds increased progressively, reaching over 80: 1 for fibres greater than 30 microns in length. Rats treated with long-fibre chrysotile developed six times more advanced interstitial fibrosis (asbestosis) than animals treated with short-fibre chrysotile and three times more pulmonary tumours. At the end of the 12-month dusting period, three times more short chrysotile than long had been retained in the rat lung tissues. During the following 6 months, however, the short-fibre chrysotile was removed from the lungs much more rapidly than the long. Following intraperitoneal injection at a mass dose of 25mg of dust, both long and short chrysotile produced mesotheliomas in more than 90% of rats. At a dose level of 2.5mg of dust, the short-fibre chrysotile produced mesotheliomas in only one-third as many rats as the long-fibre dust which still produced mesotheliomas in more than 90% of animals injected. At a dose level of 0.25mg of dust, the short-fibre chrysotile produced no mesotheliomas while the long-fibre chrysotile still produced these tumours in 66% of rats. In the two highest doses, where short-fibre chrysotile produced mesotheliomas, the mean tumour induction period was significantly longer than for tumours produced by long chrysotile.

• Fibrinolysis by rat mesothelial cells in vitro: the effect of mineral dusts at non-toxic doses. K. Donaldson, G.M. Brown, R.E. Bolton, et al. 1988;69(4):487-94. PubMed · Free full text

  Abstract

  Rat mesothelial cell cultures were shown to have considerable plasminogen dependent and independent fibrinolytic activity in vitro using an 125I fibrin degradation assay. At non-toxic doses of the mineral dusts titanium dioxide, quartz and crocidolite asbestos, as assessed by 51Cr release, the fibrinolytic activity of mesothelial cells was inhibited. Quartz had the greatest inhibitory effect and crocidolite asbestos had the least. These results suggests that inhibition of mesothelial cell fibrinolysis does not, on its own, explain pleural fibrosis due to toxic mineral dusts.

• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro. K. Donaldson, J. Slight, G.M. Brown, et al. 1988;69(3):327-38. PubMed · Free full text

  Abstract

  Inflammatory cells are recruited to the parenchyma of the lung in a range of conditions where they are considered to have the ability to exert damaging effects on elements of the alveolus. The injurious effects of rat bronchoalveolar-derived inflammatory cells on an alveolar Type II epithelial cell line were therefore assessed. Inflammatory populations produced by intratracheal injection of Corynebacterium parvum or quartz caused non-lethal detachment injury to the epithelial cells on co-culture whereas control bronchoalveolar cells had no effect on epithelial cells. The pathogenic mineral dusts quartz and chrysotile asbestos caused increased detachment injury when added to co-cultures of epithelial cells and bronchoalveolar leucocyte populations; neither titanium dioxide, a control mineral dust, nor zymosan were active in this respect. Detachment injury was particularly marked when quartz was added to co-cultures of epithelial cells and inflammatory bronchoalveolar cells from quartz treated lung. On the basis of anti-protease and anti-oxidant studies, the detachment injury was found to be mediated by protease alone in the case of quartz cells and protease plus oxidant in the case of C. parvum cells. The two inflammatory bronchoalveolar cell populations were found to have increased proteolytic activity, compared to control bronchoalveolar cells, as shown by increased ability to degrade fibronectin, laminin and denatured collagen. Inflammatory bronchoalveolar cells therefore have the potential to attack elements of the septal extracellular matrix as well as to compromise the integrity of the alveolar epithelium.

• Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process. J.M. Davis, J. Addison, R.E. Bolton, et al. 1986;67(1):113-29. PubMed · Free full text

  Abstract

  Long term inhalation studies and intraperitoneal injection studies in rats were undertaken with a series of chrysotile asbestos dusts. Three dust samples were generated from chrysotile modified by the wet dispersion process (WDC) and one was from unmodified chrysotile. Following a 1 year inhalation period, all the chrysotile samples proved extremely fibrogenic and carcinogenic and there were no significant differences between the WDC dusts and normal chrysotile. In all experimental groups approximately 25% of animals developed pulmonary carcinomas and in the oldest rats advanced interstitial fibrosis occupied on average 10% of all lung tissue. In the injection studies all the dust samples produced mesotheliomas in over 90% of animals. Very little chrysotile remained in the lungs of the animals that survived longest following dust inhalation and what there was was present as individual chrysotile fibrils. It is suggested that chrysotile is potentially the most harmful variety of asbestos as shown in these and other animal studies but that it is removed from lung tissue quite rapidly. In the long lived human species this may mean that except where exposure levels are very high and of long duration, chrysotile should be less hazardous than other asbestos types.

• The in vitro activities of a highly carcinogenic mineral fibre--potassium octatitanate. A. Poole, R.C. Brown, A.P. Rood. 1986;67(2):289-96. PubMed · Free full text

  Abstract

  The in vitro activities of a highly carcinogenic potassium octatitanate fibre (Fybex) have been investigated. This material caused a low level of in vitro transformation in C3H10T1/2 cells and is thus more active in this assay than the UICC amphibole asbestos samples but less active than fibrous erionite. This ranking is in accord with carcinogenicity in vivo. However Fybex had no detectable activity in an assay for DNA damage based on the S1-nuclease sensitivity of the DNA from exposed cells. In that assay crocidolite asbestos was more active than either of the more carcinogenic dusts. It is suggested that the activities of amphibole asbestos in assays for genetic toxicity may depend on the production of free radicals via a catalytic reaction requiring the presence of transition elements which are either not present or only present at low concentrations in erionite or Fybex. This type of reaction may not be related to in vivo carcinogenicity. The action of fibrous dusts against macrophage-like cells, measured in this instance by the release of arachidonic acid, remains one of the best measures of biological activity.

• The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection. J.M. Davis, J. Addison, R.E. Bolton, et al. 1986;67(3):415-30. PubMed · Free full text

  Abstract

  For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.

• The chemiluminescent response of human phagocytic cells to mineral dusts. I.P. Gormley, M.J. Kowolik, R.T. Cullen. 1985;66(4):409-16. PubMed · Free full text

  Abstract

  Luminol-dependent chemiluminescence (CL) was used to assess the in vitro production of reactive oxygen species by human neutrophils and monocytes on exposure to six standard respirable mineral dusts. Every dust caused CL production in both phagocytic cell types, although, for each dust, the two cells showed a different pattern of response. Light output was markedly affected by the presence of serum in the system. While the results illustrated the complexity of the interaction between mineral dusts and monocytes and neutrophils, they did not support the hypothesis that pathogenic dusts would induce the production of more reactive oxygen species than non-pathogenic dusts.

• Chemiluminescence of asbestos-activated macrophages. K. Donaldson, R.T. Cullen. 1984;65(1):81-90. PubMed · Free full text

  Abstract

  Chemiluminescence, a measure of reactive oxygen release by phagocytes, was compared in peritoneal exudate macrophages elicited with chrysotile asbestos, Corynebacterium parvum and saline. Chrysotile asbestos- and C. parvum-activated macrophages produced significantly more chemiluminescence than saline-elicited macrophages. In a second series of experiments the ability of opsonized chrysotile asbestos to act as a trigger for the release of chemiluminescence was tested. Opsonized chrysotile asbestos produced a dose-related release of chemiluminescence from activated macrophages except at the highest dose where chemiluminescence was reduced due, possibly, to a toxic effect of chrysotile during the assay. Opsonized latex also triggered a dose-related chemiluminescent response from activated macrophages. The potential role of toxic reactive oxygen species, released from macrophages, in the development of asbestos-related pulmonary inflammation and fibrosis are discussed.

• Chemotactic factor generation by asbestos. Fibre type differences and the effects of leaching. E. Yano, A. Takeuch, Y. Yukiyamo, et al. 1984;65(2):223-9. PubMed · Free full text

  Abstract

  The generation of chemotactic factors in normal human serum by treatment with chrysotile and crocidolite asbestos was investigated using the Boyden chamber method. Both types of asbestos produced chemotactic activity but not to the same extent. The two fibre types also produced different levels of complement activation as measured by C3 conversion using two dimensional immunoelectrophoresis. While there was a simple correlation between fibre concentration and C3 conversion the production of chemotactic activity declined at high doses of chrysotile. Phosphate buffer treatment reduced the differences between fibre types. The possible role of these phenomena in asbestos-associated disease is discussed.

• Fibrogenesis by mineral fibres: an in-vitro study of the roles of the macrophage and fibre length. M. Aalto, A.G. Heppleston. 1984;65(1):91-9. PubMed · Free full text

  Abstract

  Evidence on the mechanism by which inhaled mineral fibres lead to pulmonary fibrosis has not been forthcoming. As with silica, a biphasic cell culture system was required to distinguish phagocytosis from collagen formation. Synthesis of total protein and collagen by rat fibroblasts was estimated by incorporation of labelled proline after treatment with the medium from rat peritoneal macrophages that had been cultured in the presence of different types of mineral fibre. The influence of fibre length was also examined. All the main varieties of asbestos reacted with macrophages to produce or release a fibrogenic factor. However, chrysotile and the longer amosite fibres evoked the response only after prolonging the period of incubation with macrophages, presumably by permitting more complete phagocytosis of curled or longer fibres. Short amosite fibres proved to be more active than longer ones and under certain conditions were as potent as quartz. Fibrous glass also possessed stimulatory properties and again a sample having a short length gave a stronger response than a long one. Collagen formation by asbestos thus appears to be mediated by a macrophage factor, so operating in a manner similar to that previously demonstrated for quartz. The conventional view that short fibres are comparatively insignificant in asbestos fibrogenesis cannot, on the present evidence, be sustained. Furthermore, it should not be assumed than man-made mineral fibres of respirable diameter are innocuous or that short ones can be ignored.

• Intrapulmonary distribution of inhaled chrysotile and crocidolite asbestos: ultrastructural features. Y. Oghiso, E. Kagan, A.R. Brody. 1984;65(4):467-84. PubMed · Free full text

  Abstract

  Although all commercial types of asbestos can cause pulmonary fibrosis, little is known about ultrastructural differences in the evolution of pulmonary lesions induced by amphiboles and serpentines. The present study was designed to compare the histological and ultrastructural effects produced by chronic inhalation of either crocidolite (amphibole) or chrysotile (serpentine) asbestos in the rat. Animals, exposed by intermittent inhalation for 3 months, were killed after 2 to 16 months. When inhaled, both types of asbestos caused thickened alveolar duct bifurcations associated with macrophage aggregates. Crocidolite inhalation also produced subpleural collections of alveolar macrophages and lymphocytes. Electron microscopy revealed some similarities, but also distinct differences, in the pulmonary distribution of inhaled chrysotile and crocidolite. Whereas both asbestos varieties were identified within the pulmonary interstitium, only crocidolite was detected inside alveolar macrophages. Chrysotile fibres were seen infrequently within the vascular compartment. Microcalcifications were noted after chrysotile inhalation, but were never observed following crocidolite exposure. Both asbestos types induced slight pulmonary fibrosis. These findings indicate that crocidolite and chrysotile produce different pathogenetic features, although both are fibrogenic.

• Pluripotential nature of mesotheliomata induced by inhalation of erionite in rats. N.F. Johnson, R.E. Edwards, D.E. Munday, et al. 1984;65(3):377-88. PubMed · Free full text

  Abstract

  Mesotheliomata can be induced more rapidly and more frequently by inhalation of erionite than by asbestos inhalation. Erionite-induced tumours have in general a similar ultrastructural appearance to inoculum-induced pleural and peritoneal mesotheliomata. Unusual features of these tumours were the presence of dense-cored vesicles and cells staining positively for neuron-specific enolase which indicated the presence of endocrine cells. In addition, one tumour showed differentiation towards bone-forming cells. The expression of both epithelial and mesodermal characteristics demonstrates the pluripotential nature of mesothelial cells under certain circumstances.

• Failure of macrophage activation to induce pulmonary fibrosis in asbestos-exposed guinea-pigs. R.J. Emerson, P.J. Cole. 1983;64(1):66-74. PubMed · Free full text

  Abstract

  Inhalation of asbestos by specific-pathogen-free (SPF) guinea-pigs the macrophages of which were systemically activated with Freund's complete adjuvant and/or M. tuberculosis (Strain H37Ra) induced a diffuse pulmonary mononuclear-cell infiltration of the interstitium and air space. The severity of the reactions to the various insults was dependent on the treatment given. Although there was no histological evidence of increased collagen, there was a diffuse increase in reticulin in animals which were exposed to asbestos and the macrophages of which were activated. However, even in the case where severe pulmonary inflammatory changes occurred complete resolution of the response took place within 1 year. Therefore in this model activation of macrophages does not have a detrimental effect after inhalation of asbestos.

• A study of macrophage-mediated initiation of fibrosis by asbestos and silica using a diffusion chamber technique. E.D. Bateman, R.J. Emerson, P.J. Cole. 1982;63(4):414-25. PubMed · Free full text

  Abstract

  Several cellular interactions have been identified as potentially important in fibrogenesis induced by mineral dusts. Evaluation of their relative importance in vivo remains a problem. Sealed diffusion chambers limited by Nuclepore membranes and implanted into mouse peritoneal cavities provide a means of assessing different stages of fibrogenesis by separating initiating mechanisms (dust-macrophage-lymphocyte combinations inside the chamber) from the target tissue. Fibrous reactions surrounding the chambers were quantitated by macroscopic and histological scoring, and by measurement of 14C glycine incorporated at the reaction site. Using this model the fibrogenicity of Rhodesian A chrysotile asbestos, DQ12 quartz and haematite were compared. Whereas asbestos-macrophage ratios of between 6 . 6 and 900 micrograms/10(6) mouse peritoneal macrophages (MPM) produced fibrosis, an equivalent response was obtained with 0.05 micrograms silica/10(6) MPM. Silica in amounts greater than this produced macrophage cytotoxicity without fibrogenesis. Haematite-macrophage combinations produced no significant fibrosis. It was confirmed that a direct dust-macrophage interaction forms the essential first step in fibrogenesis by both asbestos and silica and that the fibrogenicity is mediated by diffusible factor(s). Prior stimulation of host mice with Freund's complete adjuvant modified the fibrogenic response to some dust-cell combinations, suggesting an important role for host responses in determining the outcome of fibrogenic stimuli.

• Reaction of cells cultured in vitro to different asbestos dusts of equal surface area but different fibre length. J.L. Kaw, F. Tilkes, E.G. Beck. 1982;63(1):109-15. PubMed · Free full text

  Abstract

  Peritoneal macrophages from mice were cultured in Leighton tubes and exposed to UICC chrysotile, crocidolite or amosite. Their cytotoxicity (Erythrosin uptake), release of lactate dehydrogenase (LDH) and uptake of 3H amino acids were determined according to weight (100 micrograms/tube), surface area (21.3 cm2 or fibre length. In all reactions tested chrysotile was more active than the amphiboles, but the latter gained activity if applied according to surface area. Uptake of 3H amino acids basis. Long-fibred asbestos dusts proved more cytotoxic than the corresponding short fibres when used on the basis of equal mass. In experiments with ascites tumour cells induced by nemalite the different asbestos dusts showed a very significant reduction of 3H-labelled thymidine uptake, but on weight basis the amphibole uptake was markedly higher.

• An ultrastructural study of the effects of asbestos fibres on cultured peritoneal macrophages. N.F. Johnson, R. Davies. 1981;62(6):559-70. PubMed · Free full text

  Abstract

  The effects of crocidolite and chrysotile fibres on lavaged peritoneal macrophages have been studied by both scanning (SEM) and transmission (TEM) electron microscopy. SEM provided little information (as the surface topography did not reflect the underlying cytoplasmic organization) except that it showed that individual macrophages often partially engulfed many long fibres in a random fashion. TEM revealed the fibres in and protruding from membrane-bound vacuoles, free in the cytoplasm and penetrating the nucleus. The cellular distribution of the fibres is discussed in terms of the cytotoxic nature of the fibres and their ability to produce a selective release of enzymes from the macrophages.

• Effects of long term inhalation of alumina fibres in rats. G.H. Pigott, B.A. Gaskell, J. Ishmael. 1981;62(3):323-31. PubMed · Free full text

  Abstract

  Groups of rats were exposed by inhalation to atmospheres containing a refractory alumina fibre (Saffil Fibres, I.C.I.) either as manufactured or in a thermally aged form. Similar groups were exposed to UICC chrysotile A asbestos or clean air to serve as positive and negative controls respectively. Exposures continued for 86 weeks after which the animals were maintained to 85% mortality. Pulmonary reaction to both forms of alumina fibre was minimal; chrysotile asbestos provoked the expected progressive fibrosis. Pulmonary tumours (both benign and malignant) were confined to rats dosed with asbestos. The results support the predicted inert nature of these alumina fibres.

• Effects of chrysotile asbestos on mononuclear cells in vitro. S. Kagamimori, M.P. Scott, D.G. Brown, et al. 1980;61(1):55-60. PubMed · Free full text

  Abstract

  Chrysotile asbestos (400 micrograms/ml) was not found to be cytotoxic towards human blood lymphocytes in culture over a 72 h period, although there was indirect evidence of cytoxicity towards plastic adherent mononuclear cells (PAM). There was significant suppression of 3H-thymidine incorporation into cells cultured with phytohaemagglutinin (PHA) in the presence of fibres. It was found even when chrysotile was added 24 h after PHA. No suppression was found for chrysotile-treated PAM-depleted cultures in comparison to control cultures. Antibody-dependent cell-mediated cytotoxicty (ADCC) was inhibited by the presence of chrysotile, and appeared to be due to prevention of contact between antibody-coated target cells and effector cells.

• The effects of intermittent high asbestos exposure (peak dose levels) on the lungs of rats. J.M. Davis, S.T. Beckett, R.E. Bolton, et al. 1980;61(3):272-80. PubMed · Free full text

  Abstract

  Four groups of rats were treated by inhalation with the UICC preparations of amosite or chrysotile in order to explore the effects of intermittent high dust concentrations (peak dosing). For each of the 2 asbestos types one group of rats was treated for 5 days each week, 7 h a day, for 1 year. Two other groups were treated with amosite or chrysotile at 5 times the previous dose for 1 day each week for 1 year. Results showed that the lung dust levels of both chrysotile or amosite in the lungs of rats after the 12-month inhalation period were similar regardless of whether "peak" or "even" dosing had been used. During the following 6 months, asbestos was cleared from the "peak" chrysotile group more slowly than the "even" chrysotile group but clearance from the "peak" amosite group was faster than that found after "even" dosing with amosite. Levels of early peribronchial fibrosis were generally lower for the "peak" dosing groups than for "even" dosing although levels of interstitial fibrosis were slightly higher following "peak" dosing. The incidence of pulmonary neoplasms did not differ between the "peak"-dosing and "even"-dosing experiments. These findings therefore give no indication that short periods of high dust exposure in an asbestos factory would result in a significantly greater hazard than would be indicated by the raised overall dust counts for the day in question.

1970s

• The histopathology and ultrastructure of pleural mesotheliomas produced in the rat by injections of crocidolite asbestos. J.M. Davis. 1979;60(6):642-52. PubMed · Free full text

  Abstract

  Primary tumours of the pleural cavity were produced in rats by the intrapleural injection of crocidolite asbestos. Their histological structure as seen with both light and electron microscopy was very variable and tumours frequently contained elements of both connective-tissue and epithelial type. In some instances the connective-tissue elements predominated from the start and the earliest tumour nodules consisted mainly of pleomorphic connective-tissue cells with only a few layers of cells more nearly epithelial in type on the surface. This pattern was largely retained when tumour nodules increased in size and coalesced, but in the deeper layers of advanced tumours the pleomorphic connective-tissue pattern was often replaced by a more uniform spindle-cell form. Other tumours were more predominantly epithelial in type, showing either a papillary pattern with rounded epithelial cells growing in solid columns, or a vesicular form in which large tissue spaces, often intracellular, were lined by very thin layers of extended cell cytoplasm. Whereas early tumours showed only one histological pattern, the more advanced stages often exhibited areas of all 3, so that there seemed to be some degree of histological mutability. The spindle-cell areas of advanced tumours frequently showed evidence of direct invasion of the surrounding tissue but this was never seen with the epithelial forms of rat mesothelioma.

  In plain English

  This was an animal experiment. Forty-eight white Han rats were each given one injection of 25 mg of crocidolite asbestos into the pleural cavity, the space around the lungs. The rats were killed 12 to 20 months later, and tumours and possible early lesions were examined with light and electron microscopes. Tumours, including very early growths confirmed only under the microscope, developed in 16 of the 48 rats (33%). The pleural mesotheliomas showed three distinct tissue patterns, visible even in the earliest lesions. One had epithelial-type cells on the surface over spindle-shaped connective-tissue cells. One was papillary, with rounded epithelial cells in solid columns. One was vesicular, with spaces lined by thin, flattened cells. Nodules under 1 mm showed only one pattern, while larger tumours often showed more than one. Spindle-cell areas often invaded the muscle of the body wall, but no invasion of lung tissue was found. Comparing these results with his earlier rat study, the author concluded that crocidolite appeared more carcinogenic in the peritoneal than the pleural cavity. He also concluded that mesotheliomas likely develop from basically mesenchymal cells.

  We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

• Biological effects of chrysolite after SO2 sorption. iii. effects on the biochemical components of alveolar washing. A. Oblin, J.M. Warnet, M.C. Jaurand, et al. 1978;59(1):32-7. PubMed · Free full text

  Abstract

  The short-term effects of chrysotile asbestos before and after SO2 sorption are studied in the rabbit after intratracheal injection of low doses of these pollutants. Chrysotile, as well as SO2-chrysotile, induces an increase in the unsaturated fatty acid content of lung surfactant, which is similar to that observed in the respiratory distress syndrome of the newborn, and an increase in the protein level of pulmonary washings which may be explained by an increase of the permeability of the blood-air barrier. These soluble proteins can interact with the surfacant and thus decrease its tensio-active properites.

• Light and electron microscope studies of the rat digestive tract following prolonged and short-term ingestion of chrysotile asbestos. R. Jacobs, J. Humphrys, K.S. Dodgson, et al. 1978;59(5):443-53. PubMed · Free full text

  Abstract

  Rats were fed diets containing 0.5 mg or 50 mg of chrysotile asbestos each day for 1 week or 14 months and tissues of the gastrointestinal tract were examined by light and electron microscopy. At the light microscope level the oesophagus, stomach and caecum in treated animals appeared unaffected, whereas accumulation of cellular debris and Alcian blue-positive material was apparent in the ileal, rectal and colonic lumens. Electron microscope examination of the colon and ileum of rats ingesting 50 mg chrysotile/day for 14 months confirmed these findings and indicated changes in the mucosal lining cells of the ileum which were consistent with a mineral-induced cytotoxicity. These results are compared with those reported in a similar previous biochemical study and the specificity of asbestos action on certain regions of the gastrointestinal tract is discussed.

• Nucleic acid metabolism in the rat following short-term and prolonged ingestion of chrysotile asbestos or cigarette-smoke condensate. R. Jacobs, M. Weinzweig, K.S. Dodgson, et al. 1978;59(6):594-600. PubMed · Free full text

  Abstract

  Rats which have ingested a natural diet containing chrysotile asbestos (50 mg/day) both in the short (one week) and long term (5-15 months) show a statistically significant increase in the incorporation of [3H]-thymidine into DNA in the small intestine mucosa, colon and rectum, stomach and spleen and a significant decrease in the incorporation of this radiolabel into liver DNA. However, short-term ingestion of similar quantities of chrysotile produced no significant change in the incorporation of [3H]-uridine into RNA in any tissues, although prolonged ingestion of the mineral induced alterations in RNA metabolism in the lung and liver. By contrast, animals ingesting a natural diet containing cigarette-smoke condensate show a significantly high incorporation of [3H]-uridine into RNA in the mucosa, submucosa, spleen and heart following short-term exposure. Long-term ingestion of this diet produces similar changes in the submucosa, spleen and lung. The apparent specificity and the mechanism whereby ingested chrysotile interferes with DNA metabolism in some body tissues is discussed.

• The cytotoxic effects of asbestos and other mineral dust in tissue culture cell lines. M. Chamberlain, R.C. Brown. 1978;59(2):183-9. PubMed · Free full text

  Abstract

  The cytotoxic effects of 15 dusts have been tested in 2 cell lines. Experimental animal data are available for 11 of the 15 dusts. There is a correlation between the cytotoxic activities of the dusts and the ability to induce mesothelial tumours following intrapleural injection of the dusts. Some preliminary observations on the nature of interaction between the dusts, medium components and the cells are reported. It is suggested that the study of the interactions between cells and dusts in culture may lead to an understanding of the pathogenesis of these dusts in man and animals.

• A preliminary study of biochemical changes in the rat small intestine following long-term ingestion of chrysotile asbestos. R. Jacobs, K.S. Dodgson, R.J. Richards. 1977;58(5):541-8. PubMed · Free full text

  Abstract

  Changes are reported in the DNA, RNA, protein and brush border enzymes in the small intestine mucosal lining cells and gut lumen, induced by maintaining rats on a diet containing chrysotile asbestos for 10 months. Intracellular levels of RNA, DNA and protein remained unchanged but significant alterations, consistent with a mineral-induced cytotoxicity, were found in the lumen level of DNA (increased) and RNA (decreased) in asbestos-treated rats. Most intracellular enzyme levels were consistently, but not significantly, elevated in animals maintained on diets containing asbestos whilst the activities within the lumen were significantly higher than those found in normal animals. The presence of cigarette smoke alone in the diet induced changes in intracellular RNA and lumen ATPase but the combined effect of cigarette smoke and asbestos was rarely different from the alterations induced by asbestos alone on the majority of parameters studied.

• The biological effects of magnesium-leached chrysotile asbestos. A. Morgan, P. Davies, J.C. Wagner, et al. 1977;58(5):465-73. PubMed · Free full text

  Abstract

  Chrysotile asbestos was leached in N hydrochloric acid for varying times to produce a range of magnesium-depleted samples. The protein adsorptive capacity, the haemolytic activity, and the capacity to cause selective release of acid hydrolases from macrophages were measured for the various samples in vitro. The carcinogenicity of the same materials was determined following intrapleural inoculation in rats. The adsorptive capacity for albumin decreased linearly with magnesium removal. The haemolytic activity also declined until about half the magnesium had been removed, after which there was little further change. The selective release of acid hydrolases from macrophages in culture increased up to the point at which half the magnesium had been removed but by 90% depletion had declined rapidly. The carcinogenicity of 50% -depleted chrysotile was similar to that of intact, but at 90% depletion the incidence of mesothelial tumours had fallen considerably. There was no evidence that the leached samples fragmented more than the unleached in vivo.

• The effects of long-term exposure of lung fibroblast strains to chrysotile asbestos. P.M. Hext, J. Hunt, K.S. Dodgson, et al. 1977;58(2):160-7. PubMed · Free full text

  Abstract

  Evidence is presented that persistent long-term exposure of a strain of lung fibroblast-like cells to chrysotile asbestos over 37 passages in vitro leads to enhancement in cell mat collagen deposition and is accompanied by other metabolic alterations in the cultures.

• The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation. H.U. Schorlemmer, P. Davies, W. Hylton, et al. 1977;58(3):315-26. PubMed · Free full text

  Abstract

  The paralelism between the capacity of various agents to elicit chronic inflammatory responses in vivo and to induce the selective release of lysosomal enzymes from cultures of mouse peritoneal macrophages in vitro is discussed. Zymosan elicits an intense inflammatory response when injected i.m. in mice. Chrysotile asbestos produces a response of a similar nature and intensity as is seen with zymosan, while injections of acid-leached asbestos and polystyrene latex are not followed by inflammation. It is also shown that zymosan and asbestos induce a dose-dependent increase in the total enzyme activity of an inflamed muscle. On the other hand latex and acid-leached asbestos caused no significant increases in lysosomal enzyme levels. Agents eliciting inflammatory responses, such as zymosan and chrysotile asbestos induce a selective release of acid hydrolases from cultured macrophages; in contrast agents lacking the capacity to induce inflammation, such as latex and acid-leached chrysotile asbestos, do not induce the release of lysosomal enzymes from cultured macrophages.

• Biochemical effects of asbestiform minerals on lung fibroblast cultures. P.M. Hext, R.J. Richards. 1976;57(3):281-5. PubMed · Free full text

  Abstract

  The ability of different types of asbestiform minerals to enhance or suppress the levels of fibrous collagen in cultures of lung fibroblasts was tested. All commercially important asbestos dusts produced both effects, a lower dose favouring a fibrogenic response whereas a higher dose favoured an opposite effect.

• Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats. T.D. Tetley, P.M. Hext, R.J. Richards, et al. 1976;57(5):505-14. PubMed · Free full text

  Abstract

  Rats inhaling chrysotile asbestos contracted asbestosis and fibrosis of the lungs. Studies of biochemical and morphological changes (between normal and treated animals) show that chrysotile induces an increase in the lung free cell population and pulmonary surfactant levels. Lysosomal enzyme levels are elevated in both the whole lung and free cell population and there are considerable changes in macrophage morphology. It is suggested that the primary response of the lung to chrysotile is an increase in surfactant production coupled with an increase in free cell numbers, in order to prevent the cytotoxic effect of the dust.

• An electron microscope study of the response of mesothelial cells to the intrapleural injection of asbestos dust. J.M. Davis. 1974;55(1):64-70. PubMed · Free full text

  Abstract

  Studies of the pleural mesothelium in rats, mice, and guinea-pigs following the intrapleural injection of asbestos dust, showed that for 6 months at least this dust did not induce mesothelial hyperplasia. During the first few days after injection some areas of mesothelial cells became rounded and less clearly attached to one another, and a few were found to contain small numbers of asbestos fibres. During this period there was evidence of the penetration of asbestos fibres between the mesothelial cells, into the submesothelial connective tissues. Later in the studies the mesothelium covering most of the pleural cavity returned to normal, but where mesothelium covered asbestos granulomata, the cells were found to be extremely flattened, and without surface microvilli. Usually the mesothelial covering was complete, but in some areas pores were found penetrating the mesothelial cell cytoplasm and leaving areas of connective tissue in direct contact with the pleural cavity. In a few cases mesothelial cells were found lining clefts within the connective tissue of asbestos granulomata.

• Radiological diagnosis of crocidolite induced pleural mesotheliomata in the rat. M.S. McLachlan, J.C. Wagner. 1974;55(2):164-8. PubMed · Free full text

  Abstract

  Crocidolite asbestos dust was inoculated intrapleurally in 36 rats. Chest radiographs were obtained up to 120 weeks after inoculation. Radiological and pathological observations were compared. In 3 animals, in which mesotheliomata were suspected radiologically, no evidence of malignancy was observed on histological examination. A radiological diagnosis suggesting probable or definite malignancy was made in all 7 animals with histologically proven mesotheliomata.

• Ultrastructural changes in lung fibroblast cultures exposed to chrysotile asbestos. R.J. Richards, P.M. Hext, G. Blundell, et al. 1974;55(3):275-81. PubMed · Free full text

  Abstract

  Early changes in the ultrastructure of lung fibroblasts exposed to chrysotile asbestos in vitro are described. The dust exposed cells rapidly undergo a “maturation process” reflected by highly dilated endoplasmic cisternae, irregularity in nuclear outline and composition and the appearance of membrane microvilli which are all characteristics of normal cells in the stationary phase. It is suggested the surviving cells undergoing this “maturation process” may account in part for the higher synthetic activity, leading to increased collagen levels, in chrysotile exposed cultures.

• Some biochemical effects of asbestos on macrophages. K. Miller, J.S. Harington. 1972;53(4):397-405. PubMed · Free full text

  Abstract

  The in vitro effects of chrysotile, crocidolite and amosite asbestos, and silica and rutile dust, on hamster peritoneal macrophages were assessed by estimating the release of acid phosphatase into the culture medium and by changes in the composition of phospholipids in the cells. Chrysotile was as toxic as silica, while crocidolite, amosite and the control dust, rutile were inert. The toxicity of chrysotile and silica is evidently due to the surface interaction of the dusts with phagosomal membranes, leading to the release of lytic enzymes from the damaged phagosomes into the cytoplasm. Considerable amounts of acid phosphatase were released into the medium 28 hours after the phagocytosis of both dusts, whereas very little was found when crocidolite, amosite and rutile were used. Further evidence of cytopathic effects was seen by changes in lipid components of cells which had ingested silica and chrysotile. A decrease in total lipid content and an increase in lysolecithin apparently indicate specific, secondary and toxic effects following the release of lysosomal enzymes.

• The effects of inhaled crocidolites from Transvaal and North-west Cape mines on the lungs of rats and guinea-pigs. S.K. Botham, P.F. Holt. 1972;53(6):612-20. PubMed · Free full text

  Abstract

  A group of guinea-pigs and another of rats were successively placed for 400 hours in an atmosphere containing a high concentration of North-west Cape (NWC) crocidolite fibres. A further group of guinea-pigs inhaled Transvaal (TVL) crocidolite for an equal time. Guinea-pigs that inhaled NWC crocidolite were substantially outlived by animals of the other 2 groups, of which the longest survivors were 2 guinea-pigs. No mesotheliomata were found but in all the lungs cellular proliferation of the septa caused a reduction in alveolar space. Giant cells were common and asbestos bodies developed in guinea-pigs, but in rats only a very few, atypical asbestos bodies were seen, and giant cells were rare. All lungs contained uncoated fibres, long fibres (occasionally exceeding 50 μm) being seen in subpleural regions in older animals and in peribronchiolar accumulations. NWC fibres reached the muscular coats of larger bronchioles of guinea-pigs sooner than TVL crocidolite. Proliferation of bronchiolar epithelium was produced in guinea-pigs and 2 rats by NWC crocidolite, but not by TVL crocidolite. Guinea-pigs dying over 3 months and rats over 18 months after inhalation of NWC crocidolite had several small emphysematous regions at the lung periphery, but only one small area was seen in each of the last 2 guinea-pigs that inhaled TVL fibres. Thus, NWC crocidolite produced greater disruption of the respiratory surfaces. Severe lung fibrosis was not seen, although fine collagen strands were found in interalveolar septa of animals dying at over 5 months after dusting began. Dense subpleural areas of collagen produced by TVL crocidolite were, however, found in the 4 oldest guinea-pigs. Inhalation of these 2 crocidolites results in different pathological responses, although no difference in distribution in the lung were found to explain differences in survival time, bronchiolar epithelial proliferation or subpleural collagen formation.

• The effects of polyvinyl pyridine-N-oxide (P204) on the cytopathogenic action of chrysotile asbestos in vivo and in vitro. J.M. Davis. 1972;53(6):652-8. PubMed · Free full text

  Abstract

  A series of experiments was undertaken to test the action of polyvinyl pyridine-N-oxide (P204) on the cytopathic effects of chrysotile asbestos dust in experimental animals. Organ culture studies were undertaken using pieces of guinea-pig lung, and in addition to this the lesions produced by the intrapleural injection of chrysotile were studied after treatment with varying doses of P204. The results from both series of experiments were unfortunately negative and P204 appeared unable to modify asbestos lesions in any way. These findings contrast sharply with the marked ability of P204 to protect tissues from the effects of silica dust. It is suggested that these differences are due to the fact that while silica is rapidly toxic to macrophages, asbestos is not and many healthy macrophages and giant cells can be found in asbestos lesions packed with dust several weeks after injection. The fibrous tissue that is eventually produced in response to asbestos dust is probably produced by a slower and more insidious process than that stimulated by silica, and this process is not modified by the presence of P204.

• The calcification of fibrous pleural lesions produced in guinea-pigs by the injection of chrysotile asbestos dust. J.M. Davis. 1971;52(3):238-43. PubMed · Free full text

  Abstract

  In guinea-pig pleural granulomas produced by the injection of chrysotile asbestos dust, the initial cellular lesions were replaced by old acellular fibrous tissue within 15-18 months. After this period calcification of the fibrous tissue commonly occurred. The first sign of calcification was always the formation among the collagen fibres of large numbers of spherical lamellated bodies. These structures stained positive for acid mucopolysaccharides, and electron-microscope observations showed that they were formed around a core of asbestos dust. Calcium in the form of apatite crystals was also often present in these structures. Shortly after the formation of lamellar bodies the mucopolysaccharide normally present on the collagen fibres, was removed and instead it formed a thick coating around any free asbestos dust in the fibrous area. The first signs of general calcium deposition were seen both in contact with collagen fibres and on the surface of the coated asbestos dust. Eventually calcium deposits filled all the tissue spaces and enclosed collagen, coated asbestos dust and lamellar bodies in a solid mass of calcification.

• The long term fibrogenic effects of chrysotile and crocidolite asbestos dust injected into the pleural cavity of experimental animals. J.M. Davis. 1970;51(6):617-27. PubMed · Free full text

  Abstract

  In a series of experiments on the effects of chrysotile and crocidolite asbestos dust injected into the pleural cavities of experimental animals, the following results were obtained. Both dusts produced large granulomas in all the species used, but the histological patterns of these lesions varied. In guinea-pigs both chrysotile and crocidolite produced granulomas that consisted mainly of giant cells, mixed with a few macrophages and fibroblasts, and each granuloma was surrounded by a distinct capsule of fibrous tissue. In mice and rats, however, relatively few giant cells were present in the asbestos granulomas, and the lesions consisted only of macrophages with some fibroblasts. In these 2 species the granulomas were not surrounded by a distinct capsule. In all cases the granulomas were eventually replaced by masses of fibrous tissue, but the time sequence of this change was variable. In guinea-pigs the granulomas remained cellular for 6-12 months, and after this period there was evidence of the invasion of the lesions by fresh macrophages which rephagocytosed dust left behind by the death of previous cells. In mice some areas of the granulomas remained cellular for 12-15 months, but others were completely fibrosed by 6-9 months. In rats fibrosis of the asbestos granulomas was very rapid, and most lesions consisted of old almost acellular collagen by 3-4 months. In all species a few animals showed massive pleural fibrosis outside the main granulomas. In some cases this appeared to be associated with an infection spreading from the lung tissue, but in others no such association could be traced.

1960s

• The effects of chrysotile asbestos dust on lung macrophages maintained in organ culture. An electron-microscope study. J.M. Davis. 1967;48(4):379-85. PubMed · Free full text

  Abstract

  Chrysotile asbestos dust was injected into small pieces of adult guinea-pig lung maintained in organ culture for 10-14 days. This dust was taken up by the lung macrophages in a matter of hours, but dust was not found in any of the other cells during the course of these experiments. The macrophages in contact with dust produce elongated phagocytic processes on the cell surface and these encircle the dust and fold back onto the cell to form phagocytic vacuoles or phagosomes. The dust may remain in the phagosomes for some time or it can quickly escape into the cytoplasm perhaps by mechanical action. If the dust remains in a phagosome this eventually contracts to form a small dense structure usually called a residual body. In the cultured lung it was found that dust containing macrophages could quickly combine to form giant cells, and quite large specimens were often found within 24 hr. Some macrophages eventually become converted into fibroblasts with asbestos dust still retained in the fibroblast cytoplasm.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• The ultrastructure of asbestos bodies from guinea-pig lungs. J.M. Davis. 1964;45(6):634-41. PubMed · Free full text

  Abstract

  The ultrastructure of the asbestos body has been examined in guinea-pigs treated with asbestos dust by the method of Holt and Young (1960). The first sign of asbestos body formation was the accumulation of dense granules approximately 60 A in diameter around the asbestos fibre. It is suggested that these granules are ferritin material. Usually the asbestos body coating consists of a single dense layer of ferritin, but sometimes low density layers are present that contain few ferritin granules. Often a whole series of layers is built up, but there is seldom any regularity in the thickness or density of these layers. The outermost zone of these bodies often consists of an irregular layer of radially arranged fibrous material but occasionally almost the whole body coat consists of these fibres which have a diameter of 50-60 A. A few asbestos bodies were found with a segmented appearance, but it seemed likely that this was due to the deposition of the ferritin as separate globules along the length of the asbestos fibre rather than as a smooth coating. There was no evidence of the breakup of asbestos bodies in guinea-pig lungs. In addition to the traditional asbestos body consisting of a neat core of asbestos fibre surrounded by coating material, a new structure was found that consisted of an irregularly shaped aggregate of ferritin around small scattered particles of asbestos dust. These structures often contained foreign material such as carbon particles in addition to the asbestos dust and ferritin. The significance of these new structures in relation to the classical asbestos bodies is as yet uncertain.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• The ultrastructure of asbestos bodies from human lung. J.M. Davis. 1964;45(6):642-6. PubMed · Free full text

  Abstract

  In a study of asbestos bodies from human lung tissue it was found that the body structure was very similar to that previously found in asbestos bodies from guinea-pig lungs. The coating material was found to consist mainly of fine granules approximately 60 A in diameter, and it is suggested that these are ferritin material. The coats of some bodies contained layers of varying density, but this was much less commonly found than it had been in guinea-pig material. Some human bodies contained fine needle-like particles approximately 60 A in diameter embedded in the coating material, and it is suggested that these may be finely divided amosite asbestos. From the evidence of this study it would appear that the well known segmentation of asbestos bodies can be of two types. In one the segmented appearance is due to the deposition of the body coating in separate globules, and in the other it is due to the splitting of a previously smooth coat. In addition to the traditional asbestos body consisting of a neat core of asbestos fibre surrounded by coating material a new structure was found that consisted of an irregularly shaped aggregate of ferritin in which were embedded small scattered particles of asbestos dust as well as other foreign material such as carbon particles.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• An electron microscopy study of the effect of asbestos dust on the lung. J.M. Davis. 1963;44(4):454-64. PubMed · Free full text

  Abstract

  In a series of experiments on the effect of chrysotile asbestos dust on rat and guinea-pig lungs, it was found that pathological changes occurred in 3 successive stages. The first involved the formation of small nodular giant cell lesions usually in the walls of terminal bronchioles. Later a fibrosing interstitial pneumonia was found scattered widely throughout the lung and this was often followed by complete lung consolidation in some areas. It was found that in rats removed from the dust tunnel for some weeks, the consolidation tended to resolve, but no signs of resolution were seen in guinea-pigs during these experiments. Chrysotile dust was seen only in alveolar macrophages, and it would appear that no other cell types are able to phagocytose this material. It was found that giant cells were formed by the aggregation of dust-carrying macrophages, and it was also found that these macrophages can undergo conversion to fibroblasts. The chrysotile dust found in the animal lungs varied in size from fibres 10 μ long and 2 μ in diameter, to individual crystals less than 1 μ long and only about 200A in diameter. After some months in the lung some of the dust showed structural changes that may indicate that it was being dissolved by the body fluids. An aggregation of ferritin material around particles of chrysotile was commonly found, and this may be associated with the formation of asbestos bodies. Most of the capillary walls in the dusted lungs were normal in structure, but in a few cases the blood-air barrier was found to be much thicker than normal. Where this occurred the basement membrane was found to be very uneven in outline, and numerous impocketings were seen in the cytoplasm of both the epithelial and endothelial cells.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

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