Host and environmental factors enhancing carcinogenesis in the respiratory tract

Our plain-English summary of Host and environmental factors enhancing carcinogenesis in the respiratory tract, by P. Nettesheim, D.C. Topping, R. Jamasbi (Annual Review of Pharmacology and Toxicology, 1981).

The study

• Authors: P. Nettesheim, D.C. Topping, R. Jamasbi
• Journal: Annual Review of Pharmacology and Toxicology
• Published: 1981;21:133-63
• Type of article: Review
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 002569).

In plain English

This article was a review. The authors described about ten years of their own laboratory's animal and cell-culture studies, along with work by other investigators, on factors that may increase cancer of the respiratory tract. Topics included age, temporary immune suppression, dietary vitamin A, respiratory infections, tumor promoters, "inert" carrier particles, nickel subsulfide, benzo(e)pyrene and irritant gases. In the section on chrysotile asbestos, the authors described their own studies in grafted tracheas. A dose of 2 mg of chrysotile produced squamous carcinomas in 5% of tracheas. The authors concluded that asbestos must be considered a weak but definite carcinogen for the lining of the conducting airways. Some tracheas were first exposed to low doses of the chemical carcinogen DMBA and then to 200 micrograms of asbestos. Carcinomas occurred in 6 of 40 tracheas given 50 micrograms of DMBA and 9 of 40 given 25 micrograms. Tracheas given those DMBA doses alone had none (0 of 34 and 0 of 38). The authors suggested chrysotile may have a "promotion-like" effect. They noted that laboratory studies can rarely, if ever, prove the importance of specific factors in human lung cancer.

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 of the authors' own laboratory studies (animal experiments and tracheal organ cultures) and of work by other investigators
• Who was studied: For the asbestos work: tracheas grafted under the skin of laboratory animals (the tracheal transplant model, used with rats elsewhere in the review), about 34 to 40 tracheas per group in the two-stage experiment. Other sections covered rats, mice, hamsters and cultured tracheal tissue.
• Exposure: Chrysotile asbestos placed inside grafted tracheas: 2 mg alone, or 200 micrograms after a 4-week exposure to the chemical carcinogen DMBA (12.5, 25, 50 or 100 micrograms). The review also covered other agents, including DMBA, TPA, vitamin A levels, respiratory infections, carbon and iron oxide particles, nickel subsulfide, benzo(a)pyrene, benzo(e)pyrene, sulfur dioxide, nitrogen dioxide and aldehydes.
• Main results:
  • 2 mg of chrysotile alone produced squamous carcinomas in 5% of grafted tracheas. Carcinomas had never been seen in untreated or vehicle-treated transplants.
  • Tracheas given 25 micrograms of DMBA followed by asbestos had carcinomas in 9 of 40 (23%), compared with 0 of 38 for 25 micrograms of DMBA alone.
  • Tracheas given 50 micrograms of DMBA followed by asbestos had carcinomas in 6 of 40 (15%), compared with 0 of 34 for 50 micrograms of DMBA alone.
  • No increase was seen at 100 micrograms of DMBA, a dose that by itself caused 18% tracheal carcinomas (7 of 38; 9 of 40 with asbestos). No increase was seen at 12.5 micrograms (1 of 36 alone, 1 of 40 with asbestos). Asbestos alone at 200 micrograms gave 0 of 40.
  • The asbestos dose used after DMBA was one tenth of the dose needed to cause a low tumor incidence by itself.
• The authors' conclusion: The authors concluded that chrysotile asbestos must be considered a weak but definite carcinogen for the epithelium of the conducting airways. They suggested it may also have a promotion-like effect on tracheas previously exposed to another carcinogen.
• Limitations the authors state:
  • The authors stated that laboratory studies like these can rarely, if ever, prove the importance of specific factors in causing lung cancer in particular urban or occupational settings.
  • The radioactive tracing method used to follow chrysotile in the tracheal grafts underestimated how much asbestos persisted, because metal ions leached from the fibers.
  • In discussing retinoids (vitamin A-related compounds), the authors suggested that promotion may not be an important factor in the respiratory tract cancer models then in use. They saw this as a possible serious shortcoming, because promotion factors are almost certain to play a decisive role in human lung cancer.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis.

Related studies

• Tests for effect of asbestos on benzo[a]pyrene carcinogenesis in the respiratory tract — L. Miller, W.E. Smith, et al. (1965)
• Respiratory carcinogenesis: an epidemiologic appraisal — J.F. Fraumeni (1975)
• Environmental and occupational risk factors for lung cancer — I. Brüske-Hohlfeld (2009)
• Solitary fibrous tumor of the upper respiratory tract. A report of six cases — G.B. Witkin, J. Rosai (1991)
• Asbestos: mechanisms of toxicity and carcinogenicity in the respiratory tract — B. Mossman, W. Light, et al. (1983)
• In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts — B.T. Mossman (1983)

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