Small animals in the study of pathological effects of asbestos

Our plain-English summary of Small animals in the study of pathological effects of asbestos, by P.F. Holt (Environmental Health Perspectives, 1974).

The study

• Author: P.F. Holt
• Journal: Environmental Health Perspectives
• Published: 1974;9:205-11
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 mum long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal. THIS CLEARANCE MECHANISM IS INHIBITED BY OTHER FACTORS: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly. The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs.

In plain English

This 1974 article reviewed the difficulties of studying asbestos-related cancer and lung scarring (fibrosis) in small animals. It also described exploratory guinea pig experiments by the author's group. The group had not found nodular fibrosis when specific pathogen-free rats and guinea pigs, bred free of certain infections, inhaled any type of asbestos. Earlier experiments had produced fibrosis in animals with lung infections. The author described how lung scavenger cells (macrophages) coat long fibers to form asbestos bodies, which later break up and dissolve. In the experiments, guinea pigs inhaled silica dust for 200 hours or carbon dust for 400 hours, then anthophyllite asbestos for 10 hours. In silica-exposed animals, asbestos body formation was almost completely inhibited, and many uncoated fibers were visible. Very few asbestos bodies were found in carbon-exposed lungs, compared with many in animals given asbestos alone. The author suggested that uncoated long fibers presumably remain pathogenic. The author also noted that small animals may live too short a time to show cancer from inhaled asbestos. The author concluded that studying the macrophage's protective role had given encouraging results.

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: Review and commentary on animal studies of asbestos, including brief reports of the author's group's own exploratory inhalation experiments in guinea pigs
• Who was studied: Specific pathogen-free (SPF) guinea pigs at the University of Reading, England. The text does not state the total number. Table 1 lists animals numbered 1 to 10.
• Exposure: There were three groups. One inhaled silica (quartz) dust for 200 hours and then anthophyllite asbestos for 10 hours. One inhaled carbon dust at high concentrations for 400 hours and then anthophyllite asbestos for 10 hours. Controls inhaled anthophyllite asbestos only.
• Main results:
  • In guinea pigs that first inhaled silica, formation of asbestos bodies was almost completely inhibited, although many uncoated asbestos fibers were visible.
  • Very few asbestos bodies were found in lungs that also contained carbon. Many asbestos bodies were visible in control lungs from animals given asbestos only.
  • In the group's later experiments with SPF rats and guinea pigs, nodular fibrosis did not result from inhaling any type of asbestos. In earlier experiments, fibrosis occurred in animals that had lung infections.
  • After a small inhaled amount of asbestos, all long fibers visible by phase contrast microscopy were coated within 18 months. With heavier doses, some fibers remained uncoated for long periods.
  • In the author's group's earlier work, chrysotile and crocidolite inhaled by guinea pigs produced marked proliferation of the bronchiolar lining, a condition that may precede cancer.
• The authors' conclusion: The author concluded that animal study of asbestos pathology needs better than subjective assessment. The author also concluded that studying the protective role of the macrophage, which can be assessed objectively, had given encouraging results.
• Limitations the authors state:
  • The life span of small animals may be too short for cancer from inhaled asbestos to be demonstrated.
  • Assessment of early tissue changes has so far been subjective.
  • Lung fibrosis produced by injecting asbestos into the windpipe of SPF animals is probably an artifact of the method.
  • Similar effects of infection and tobacco smoke were proposed but not yet demonstrated.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Mesothelioma, Carcinoma, Asbestos Bodies, Fibrosis, Collagen, Macrophage, Bronchus.

Related studies

• Experimental asbestosis with four types of fibers: importance of small particles — P.F. Holt, J. Mills, et al. (1965)
• The long term fibrogenic effects of chrysotile and crocidolite asbestos dust injected into the pleural cavity of experimental animals — J.M. Davis (1970)
• Electron-microscope studies of asbestosis in man and animals — J.M. Davis (1965)
• Transport of inhaled dust to extrapulmonary sites — P.F. Holt (1981)
• Comparison of effects of glass fibre and glass powder on guinea-pig lungs — S.K. Botham, P.F. Holt (1973)
• Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2015)

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