Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats

Our plain-English summary of Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats, by E. Fasske (Respiration; International Review of Thoracic Diseases, 1988).

The study

• Author: E. Fasske
• Journal: Respiration; International Review of Thoracic Diseases
• Published: 1988;53(2):111-27
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Longitudinal light and electron microscopy investigations were previously carried out on Wistar rats to study the pathogenesis of pulmonary fibrosis due to asbestos. In the present study, the genesis of pulmonary carcinomas and pleural mesotheliomas have been investigated by light and electron microscopy on the same model after intrabronchial instillation of chrysotile B and benz(a)pyrene, as well as a combination of the two carcinogens. A single instillation of 1 mg chrysotile B with a fiber length between 0.05 and 0.2 micron in 0.1 ml tricaprylin by means of a polyvinyl catheter into the right lower lobe of the lung of 70 anesthetized 6-week-old Wistar rats caused pulmonary carcinomas or malignant pleural mesotheliomas in 18 animals (24%). The tumors occur at intervals between 12 and 31 months after the asbestos application. By electron microscopy, small asbestos fragments can be detected under the pleural mesothelium at the earliest 1 year after the intrabronchial application of chrysotile. A single combined instillation of 1 mg chrysotile and 0.5 mg benz(a)pyrene does not increase the tumor incidence. With simultaneous administration of these two substances, however, lung tumors arise very much earlier than in instillation of only one of the carcinogens. Thus, an adenocarcinoma was found in the lungs after 4.5 months, and a pleural mesothelioma was already found after 7.7 months. The intrabronchial instillation of benz(a)pyrene alone causes fewer lung tumors (tumor incidence 10%, interval between 13 and 33 months).

In plain English

This was an animal experiment from the Division of Pathology at the Borstel Research Institute in Germany. Six-week-old Wistar rats of both sexes, in three groups of 80, each received a single dose by catheter into the right lower lung lobe. One group got 1 mg of milled Canadian chrysotile B with fibers 0.05 to 0.2 micrometres long. A second got the same chrysotile plus 0.5 mg benz(a)pyrene, and a third got benz(a)pyrene alone. Two rats per group were killed at monthly intervals and examined by light and electron microscopy. Of 70 evaluated chrysotile-only rats, 18 (reported as 24%) developed malignant tumors between 12 and 31 months: 16 lung adenocarcinomas, one small-cell carcinoma and one pleural mesothelioma. In the combined group, 16 of 78 rats (20%) developed tumors, not more often but earlier, the first at 4.5 months. In the benz(a)pyrene-only group, 10 of 78 (13%) did, between 14 and 33 months. Asbestos fragments were seen at the visceral pleura only from 12 months. The author concluded that adding benz(a)pyrene did not raise the tumor rate but made tumors appear earlier. The author stated that the tumor numbers were too small for statistical analysis.

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.

What the study did and found

• Design: Animal experiment: longitudinal light and electron microscopic study in rats, with three treatment groups and animals killed at monthly intervals
• Who was studied: Wistar rats of both sexes, 6 weeks old, bred at the Borstel Research Institute (Germany). There were 80 rats per group. 70 were evaluated in the chrysotile-only group (10 died of pneumonia) and 78 in each of the chrysotile plus benz(a)pyrene and benz(a)pyrene-only groups.
• Exposure: A single intrabronchial instillation, by catheter into the right lower lung lobe, in 0.1 ml tricaprylin. Group 1 received 1 mg milled Canadian chrysotile B (fiber length 0.05 to 0.2 micrometres). Group 2 received 1 mg chrysotile B plus 0.5 mg benz(a)pyrene. Group 3 received 0.5 mg benz(a)pyrene alone.
• Main results:
  • Chrysotile-only group: 18 of 70 surviving rats developed a malignant tumor (printed as 24%). The tumors were 16 lung adenocarcinomas, one small-cell undifferentiated carcinoma and one pleural mesothelioma.
  • Chrysotile-only group: one adenocarcinoma and one pleural mesothelioma were found at 12 months. The remaining 16 tumors appeared between 17 and 31 months.
  • Chrysotile-only group: one rat also had a hypernephroid carcinoma of the kidney at 30 months. No asbestos was found in that kidney, and the author considered a spontaneous tumor probable.
  • Chrysotile plus benz(a)pyrene group: 16 of 78 surviving rats (20%) developed a malignant lung tumor.
  • Chrysotile plus benz(a)pyrene group: tumors were not more frequent but appeared earlier. There was an adenocarcinoma at 4.5 months and a pleural mesothelioma at 7.7 months.
  • Benz(a)pyrene-only group: 10 of 78 surviving rats (13%) developed a malignant tumor between 14 and 33 months. These were 2 pleural mesotheliomas, 1 peritoneal mesothelioma, 1 small-cell carcinoma and 6 adenocarcinomas.
  • By electron microscopy, small fragments of chrysotile fibers were found at the visceral pleura no earlier than 12 months after instillation. Asbestos fibers were not found in lung lymph nodes or large body organs at any stage.
  • The author reported that spontaneous lung cancers do not occur in this inbred rat strain. On that basis the author designated the lung and pleural tumors found as asbestos tumors.
  • In transplantation experiments, a transplanted pleural mesothelioma changed to a sarcoma after five passages. A transplanted small-cell carcinoma kept its appearance. No metastases occurred.
• The authors' conclusion: The author concluded that combining chrysotile with benz(a)pyrene did not raise the rate of lung carcinomas and pleural mesotheliomas in Wistar rats compared with asbestos alone. The author also concluded that the combination led to earlier occurrence of tumors than either substance alone.
• Limitations the authors state:
  • The author stated that the number of tumors was too small for statistical analysis. The tables only list findings and contain no statistical evaluation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chrysotile, Pulmonary Fibrosis, Carcinoma, Pleural Mesothelioma, Fiber Length, Mesothelium, Adenocarcinoma.

Related studies

• Changes in numbers and dimensions of chrysotile asbestos fibers in lungs of rats following short-term exposure — V.L. Roggli, A.R. Brody (1984)
• A study of the length and diameter of fibres, in lung and in broncho-alveolar lavage fluid, following exposure of rats to chrysotile asbestos — E. Kauffer, J.C. Vigneron, et al. (1987)
• Light and electron microscope studies of the rat digestive tract following prolonged and short-term ingestion of chrysotile asbestos — R. Jacobs, J. Humphrys, et al. (1978)
• The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation — D.W. Berman, K.S. Crump, et al. (1995)
• Solitary (localized) pleural mesothelioma. A light- and electron-microscopic study — T. Kawai, K. Yakumaru, et al. (1978)
• Peripheral biphasic adenocarcinoma of the lung: light microscopic and immunohistochemical findings — P.T. Cagle, L.C. Alpert, et al. (1992)

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