An Experimental Model For Study of Carcinogenesis in the Respiratory Tract

Our plain-English summary of An Experimental Model For Study of Carcinogenesis in the Respiratory Tract, by W.E. Smith, L. Miller, J, et al (1970).

The study

• Authors: W.E. Smith, L. Miller, J, Churg
• Published: Proceedings: Symposium on Morphology of Experimental Respiratory Carcinogenesis, Oak Ridge, Tenn., December. (1970)
• Type of article: Conference paper
• Our copy: from Johns-Manville's own medical library. The article is still under copyright, so we describe it here rather than post it.

In plain English

This was an animal experiment in male hamsters. The authors put benzo[a]pyrene (BP), a cancer-causing chemical found in cigarette smoke, into the windpipe in weekly injections, either alone or mixed with chrysotile asbestos. In the main test, hamsters completing treatment received 4.5 mg of BP, or 4.5 mg of BP plus 12 mg of chrysotile, and were followed for up to 481 days. An early dose of soft chrysotile caused many acute deaths, so that dose was reduced. In the BP-alone group, tumors were mainly papillomas of the larynx, trachea and main bronchi. All but one appeared benign, and only one lung carcinoma was found. Adding chrysotile did not appreciably change tumors in those airways, but the authors reported more lung tumors and extensive asbestosis with pleural plaques. In a separate test with 6 mg of BP, 1 lung carcinoma was found among 23 hamsters given BP alone and 14 among 23 given BP plus chrysotile. The authors said the mechanism was unclear. They suggested chrysotile may have localized BP in the lungs or delayed its clearance, but they had not measured this.

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 (intratracheal injection study in hamsters)
• Who was studied: Male LVG:LAK hamsters from Lakeview Hamster Colony, Newfield, N.J., first injected at about 2 months old and followed for up to 481 days. The number of hamsters per group in the main 4.5 mg experiment is not given in the surviving text. The separate 6 mg experiment had an effective total of 23 hamsters per group.
• Exposure: Weekly intratracheal injections of benzo[a]pyrene suspended in saline with Tween 60. Over 12 injections the BP group received 4.5 mg of BP. The BP + chrysotile group received the same BP plus chrysotile (harsh and soft samples) in the first nine injections, a total of 12 mg of chrysotile. A separate test used 6 mg of BP with or without 6 mg of chrysotile, ground together in a mortar.
• Main results:
  • In the group given 4.5 mg of BP alone, all papillomas except one appeared benign, and only one pulmonary carcinoma was found.
  • In the group given 4.5 mg of BP plus 12 mg of chrysotile, there was extensive asbestosis with adenomatoid proliferation, interstitial fibrosis, emphysema and pleural plaques. The tumor counts for this group (Table 3) are missing from the text.
  • Chrysotile did not increase the yield of tumors in the larynx, trachea or extrapulmonary bronchi.
  • The yield of pulmonary carcinomas increased when chrysotile was added to BP.
  • In the separate 6 mg BP test, 1 pulmonary carcinoma was found among an effective total of 23 hamsters given BP alone. Among an effective total of 23 hamsters given BP plus chrysotile, 14 pulmonary carcinomas were found.
  • A 2.5 mg injection of soft chrysotile caused many acute deaths, apparently from airway obstruction, so later soft chrysotile doses were reduced.
• The authors' conclusion: The authors considered it unlikely that the effect was simply the addition of a weak carcinogen to a strong one. They suggested chrysotile may have localized BP in the lungs, or that tissue reactions to chrysotile may have delayed clearance of BP from the lungs.
• Limitations the authors state:
  • The authors stated that the mechanism of the increase in pulmonary carcinomas was not clear.
  • In the published discussion, the senior author said they had not measured clearance or retention of BP in the lungs.
  • In the published discussion, the senior author said asbestos and BP had always been given at the same time. Asbestos given before or after BP had not been tested.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Chrysotile, Bronchus, Carcinoma, Pleural Plaques.

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