Experimental and Toxicologic Pathology

Our medical research library holds 17 studies published in Experimental and Toxicologic Pathology (1992–2013). 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. 10 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier GmbH
• Published: 1992–2017, Germany
• Language: English
• ISSN: 0940-2993 (print), 1618-1433 (electronic)
• Continues: Experimental Pathology
• Its record in the NLM Catalog

2010s

• Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity. M. Yokohira, Y. Nakano, K. Yamakawa, et al. 2013;65(6):925-32. PubMed · Publisher

  Abstract

  Although we have previously reported that the fiber-shaped TISMO, morphologically similar to asbestos, can induce a severe mesothelial reaction in A/J mice, it is important to clarify any strain differences. In the present study, female A/J, C3H/HeN, ICR and C57BL/6 mice were therefore employed as test strains. At the beginning of the experiment, all mice underwent a left thoracotomy and direct administration of 3mg of TISMO particles suspended in 0.2 ml saline into the left thorax. The experiment was terminated after 21 weeks and all groups were sacrificed and the mesothelium and main organs were examined histopathologically. To contribute to mechanistic analysis, iron staining with Berlin blue and Turnbull's blue, and immunostaining for calretinin were also performed. The present experiment demonstrated only minor strain differences in the degree of pleural reaction to TISMO. However, there was clear variation in the iron and lymphocyte accumulation in the pleura and in the liver. This difference in response to TISMO fibers in vivo is important information when considering the development of mesothelioma as an animal model and the extrapolation to human risk from such animal studies.

  Copyright © 2013 Elsevier GmbH. All rights reserved.

1990s

• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats. K. Unfried, N. Kociok, M. Roller, et al. 1997;49(3-4):181-7. PubMed · Publisher

  Abstract

  Mutation analysis of the tumour suppressor gene p53 in tumours induced in the peritoneal cavity of rats revealed differences in the mutational pattern with regard to the carcinogenic substances applied. In tumours induced by benzo[a]pyrene a considerable amount of p53 mutations resulting in an altered protein structure could be detected. For the development of these tumours an escape from the p53 mediated cell cycle control can be assumed. However, in tumours of the same tumour type induced by crocidolite asbestos no mutations could be observed. Since there were even no spontaneous p53 mutations detectable in this tumour group, it is obvious that in these tumours the escape from cell cycle control does not take place via inactivation of p53. Therefore, it is concluded that the molecular mechanisms of carcinogenesis and tumour development in this tumour type depend on the type of carcinogen applied.

• Pulmonary cystic keratinizing squamous cell lesions of rats after inhalation/instillation of different particles. S. Rittinghausen, U. Mohr, D.L. Dungworth. 1997;49(6):433-46. PubMed · Publisher · Free full text

  Abstract

  Cystic keratinizing squamous cell lesions from three inhalation studies (Study A, B, C) and one intratracheal instillation study (Study D) in rats were reclassified and a certain number of lesions examined immunohistochemically for PCNA (proliferating cell nuclear antigen) as a marker of cellular proliferation. The following classification was used: squamous cell metaplasia with marked keratinization, keratinizing cyst, cystic keratinizing epithelioma, cystic keratinizing squamous cell carcinoma, keratinizing squamous cell carcinoma and non-keratinizing squamous cell carcinoma. In study A (inhalation of coal oven exhaust and subcutaneous injection of a high dose of DB (ah)A) 49.3% of rats developed cystic keratinizing squamous cell carcinomas. Inhalation of coal oven exhaust gas together with intratracheal instillation of crocidolite or subcutaneous injection of a low dose DB(ah)A (dibenz(ah)anthracene) resulted in cystic keratinizing squamous cell carcinomas in 23% to 24% of the rats. High incidences of cystic squamous cell carcinomas in the range of 31.9% to 76.4% were observed in rats of Study B1 after a 10-months exposure to tar/pitch condensation aerosol (different B(a)P (benzo(a)pyrene) concentrations) with added carbon black in some groups. After a 20-months exposure period to the same inhalation atmospheres (Study B2) the incidence of squamous cell carcinomas was increased up to 95.8%. Exposure of rats to various concentrations of unfiltered diesel exhaust (Study C) resulted in incidences of cystic keratinizing epitheliomas ranging from 2.5% (2.5 mg/m3) to 10.7% (7.5 mg/m3). Epitheliomas were also observed in 16.2% of carbon black and 16.0% of titanium dioxide exposed rats. Only a few cystic keratinizing squamous cell carcinomas occurred. In the intratrachel instillation study (Study D) increased incidences of cystic keratinizing epitheliomas occurred in rats exposed to native diesel exhaust particles (16.7%), high dose of extracted diesel exhaust particles (14.6%), extracted printex 90-carbon black particles (18.8%), and extracted printex 90-carbon black particles + B(a)P (18.8%). High indicences of cystic keratinizing squamous cell carcinomas were noted in rats that received 15 mg B(a)P (14.6%) or 30 mg B(a)P (72.7%) intratracheally. Immunohistochemical labeling of nuclei with PCNA demonstrated proliferative activity in one or two (and focally more than two) peripheral cell layers of cystic keratinizing epitheliomas and in more than three peripheral cell layers of cystic keratinizing squamous cell carcinomas and keratinizing squamous cell carcinomas. The wall of keratinizing cysts showed no or a weak reaction.

• An in vitro/in vivo study into the short term effects of exposure to mineral fibres. A. Clouter, C.E. Houghton, C.A. Bowskill, et al. 1996;48(6):484-6. PubMed · Publisher

• Differences in the sensitivity of hamster and rat lung cells exposed in vitro to natural and man-made fibres. M. Aufderheide, J.W. Knebel, P. Schulte. 1996;48(6):505-7. PubMed · Publisher

• Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene. J. Friemann, M. Varnai, C. Sutter, et al. 1996;48(1):13-7. PubMed · Publisher

  Abstract

  In our investigation (i.p. test), crocidolite and benzo[a]pyrene, both caused a progression from initially reactive, then autonomously transformed proliferation of myofibroblasts and undifferentiated mesenchymal cells to malignant, multidirectionally differentiated (desmin and ED-1 positive) fibro-histiocytic tumours. Immunohistochemically these tumours showed no morphological characteristics (for example co-expression of vimentin and keratin in spindle-shaped tumour cells) of human asbestos-associated malignant mesotheliomas. On the other hand many tumour cells induced by crocidolite and benzo[a]pyrene had an ultrastructural appearance resembling fibroblasts and myofibroblasts. These have been demonstrated in only a few desmoplastic and sarcomatous mesotheliomas in human beings. None of the tumours revealed the typical ultrastructural features of epitheloid or transitional mesotheliomas. Apparently, both carcinogenic substances induce the transformation of undifferentiated pluripotent mesenchymal cells in rat peritoneum, regardless of their localization in the submesothelial compartment or perivascular connective tissue (preferentially after crocidolite application) or in the connective tissue pseudocapsule of major benzo[a]pyrene containing beeswax/tricaprylin depots in the mesometrium and mesenterial fatty tissue. In this way asbestos fibres in this animal experiment do not seem to induce an arrest in differentiation of intermediate or immature mesothelial cells as supposed formerly, but rather affect undifferentiated mesenchyme cells and myofibroblasts. This is an explanation for the immunohistochemical expression of markers of muscular differentiation in these tumour cells, which is known to occur in human malignant fibro-histiocytic tumours. If supplementary immunohistochemical investigations with different keratin antibodies also fail to confirm the mesothelial differentiation of the tumours induced in our i.p. test, the decision to call them "mesotheliomas" should be reconsidered. Further immuno-transmission-electron microscopical investigations with intermediate filament or macrophage antibodies are needed to clarify whether the term malignant "fibrohistiocytic sarcoma", "mesenchymoma" or "mesothelioblastoma" would be more correct from the morphological point of view.

• Pulmonary and pleural leukocytes from F344 rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers. T.R. Gelzleichter, J.B. Mangum, E. Bermudez, et al. 1996;48(6):487-9. PubMed · Publisher

• Results of current intraperitoneal carcinogenicity studies with mineral and vitreous fibres. M. Roller, F. Pott, K. Kamino, et al. 1996;48(1):3-12. PubMed · Publisher

  Abstract

  The study includes some 50 groups of male or female Wistar rats tested in three series. Except for one untreated group and 3 vehicle control groups, the animals were injected intraperitoneally (i.p.) once or repeatedly with dust suspensions and then examined, after lifetime observation up to 30 months, for tumours in the abdominal cavity. 1 granular dust (silicon carbide), 2 asbestos dusts (crocidolite, tremolite) and 11 vitreous fibre dust samples were administered. 5 of the vitreous fibre types were fine fibre fractions from 4 commercial insulation wools and 1 experimental wool, the others were prepared by milling glass microfibres, which have, per se, a small diameter range. The dosage per rat differed over a wide range in accordance with experience from earlier studies. The lowest dose was 0.04 x 10(9) crocidolite fibres in 0.5 mg dust, and the highest amounted to 20 x 10(9) glass fibres in 1000 mg divided into 40 weekly injections. Two mesotheliomas were found in a total of 395 rats treated with saline or granular silicon carbide (250 or 1000 mg). Eleven fibre dusts produced dose-dependent mesotheliomas at rates of up to 97 %, but the calculated fibre number > 5 micrometers in length required for inducing a 25 % tumour risk differed between the fibre samples tested in the relation of 1 to about 1000. UICC-like crocidolite heads the ranking order; the glass fibre B-01, which possesses a low durability in the body, ends it together with a rather thin sample of glass fibre type B-09. The stone fibre MMVF-21 takes a high place in the ranking order, similar to the tremolite sample. The results correspond to those of earlier i.p. tests.

• Asbestos-related diseases and asbestos types used in the former GDR. W. Sturm, B. Menze, J. Krause, et al. 1995;47(2-3):173-8. PubMed · Publisher

  Abstract

  In the period from 1960 to 1990 about 1.4 million tonnes of asbestos were imported by the former German Democratic Republic (GDR) and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former counties of Magdeburg and Dresden. In the past, asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. Chrysotile was predominantly imported from the former Soviet Union, partly from Canada. Very small amounts of amphiboles came from Mozambique, but they were not processed in the counties of Magdeburg and Halle. In the German Federal State of Saxony-Anhalt, approx. 600 asbestoses, almost 2,700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas caused by asbestos were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.

• Bromo-deoxyuridine (BRDU) uptake in the lungs of rats inhaling amosite asbestos or vitreous fibres at equal airborne fibre concentrations. K. Donaldson, D.M. Brown, B.G. Miller, et al. 1995;47(2-3):207-11. PubMed · Publisher

  Abstract

  Rats were exposed, by inhalation, to target airborne fibre concentrations of 1000 f/ml (PCOM fibres by WHO criteria) of a long amosite asbestos sample and a vitreous fibre sample; the target was closely attained for both fibre samples. The size distributions of the two fibre samples was closely similar. Rats were placed in the chambers for 7 hours and then, following a further 16 hours in room air, were injected with bromo-deoxyuridine (BRDU). The presence of BRDU-positive cells in terminal bronchioles/alveolar ducts was assessed in blocks taken from various parts of the left lung, from apex to base. There were significant differences in the proliferative responses between animals but there were also significant differences between the treatments. Lungs from rats exposed to vitreous fibres showed no greater response than the controls, but there was a markedly greater proliferative response in the lungs of rats inhaling long amosite. There was a decreasing gradient of proliferative response from the apex of the lung to the base with all treatments. This could be explained by different degrees of deposition in different areas of the lung. Similar amounts of fibre accumulated in the lungs of rats exposed to the two fibre types and it is unlikely that dissolution could be important over the timescale used here. We conclude that, when amosite asbestos deposits in the lungs of rats it stimulates a proliferative response and that deposition of an equal number of similar-sized vitreous fibres has no effect.

• Consequences of long-lasting asbestos-exposure: peripheral blood parameters in shipyard workers with and without asbestosis. I. Trosić, Z. Pisl. 1995;47(2-3):212-6. PubMed · Publisher

• Macrophage phagocytic activity and cell phagocytic capacity following intratracheal instillation of a comixture of asbestos fibers. I. Trosic, M. Matausic-Pisl, D. Vucinic. 1995;47(4):238-40. PubMed · Publisher

• Supercoiled plasmid DNA as a model target for assessing the generation of free radicals at the surface of fibres. K. Donaldson, P.S. Gilmour, P.H. Beswick. 1995;47(4):235-7. PubMed · Publisher

  Abstract

  The ability of respirable amosite and crocidolite asbestos, refractory ceramic fibres (RCFs) and man made vitreous fibres (MMVFs) to cause free radical injury to plasmid, phiX174 RFI DNA was assessed. The amosite and crocidolite asbestos caused substantial damage to the DNA and, in the main, the free radicals responsible for the asbestos-mediated DNA damage were hydroxyl radicals as determined by inhibition with mannitol. Asbestos fibre-mediated damage to the DNA was completely ameliorated by the chelation of fibre-associated iron by pre-treatment of fibres with desferrioxamine-B, confirming the importance of iron in the production of free radicals. MMVFs and RCFs produced modest free radical damage to the DNA, which was prevented by mannitol but not by iron chelation.

• Superoxide anion release by alveolar macrophages exposed to respirable industrial fibres: modifying effect of fibre opsonisation. K. Donaldson, I.M. Hill, P.H. Beswick. 1995;47(4):229-31. PubMed · Publisher

  Abstract

  Phagocyte-derived free radicals are considered to play a role in fibre-related pathology and the components of the lung lining fluid could modify the surface of fibres. Therefore we examined the ability of long amosite asbestos and a range of man-made fibres to stimulate release of superoxide anion from rat alveolar macrophages when they were in their native form (unopsonised) and opsonised by incubation in rat Immunoglobulin G. We also assessed the specific amount of opsonin adsorbed to each fibre type. In the uncoated form all of the fibres produced modest amounts of superoxide release from macrophages. When they were opsonised however there was an effect on stimulation of release of superoxide that was fibre-specific. Both MMVF21 and RCF 1 were dramatically enhanced in their ability to stimulate release and this was related to a high affinity of their surface for IgG. Code 100/475 and SiC were not substantially affected by opsonisation and this was reflected in their low affinity for IgG. Long amosite had low affinity for IgG but showed dramatic enhancement of capacity to stimulate superoxide release. These fibre-specific differences in the effect of a coating of material that is found in the lung lining points out the problems of interpretation of in vitro data and more work on this important area is warranted.

• Differences in the biological effects of crocidolite asbestos and two glass fibres on epithelial lung cells. M. Aufderheide, M. Riebe-Imre, M. Straub, et al. 1994;45(8):467-72. PubMed · Publisher

• Additional atypical malignant mesothelioma after intraperitoneal injection of mineral fibres in rats. K. Kamino, H. Ernst, U. Mohr. 1993;45(2-3):65-6. Letter PubMed · Publisher

• Atypical malignant mesotheliomas with osseous and cartilaginous differentiation after intraperitoneal injection of various types of mineral fibres in rats. S. Rittinghausen, H. Ernst, H. Muhle, et al. 1992;44(1):55-8. PubMed · Publisher

  Abstract

  The histopathological appearance of malignant mesotheliomas with osseous and cartilaginous differentiation is described in detail. Bone and cartilage occurred in mixed and sarcomatoid mesotheliomas which were induced by intraperitoneal injection of various types of asbestos fibres (asbestos cement, crocidolite, UICC-amosite, UICC-chrysotile B, Calidria-chrysotile). Bone or cartilage were found in 32.7% of mixed mesothelioma and in 12.8% of sarcomatoid mesotheliomas.

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