Hyperplastic and Neoplastic Changes in the Lungs of Rats Treated Concurrently with Chrysotile Asbestos and N-Nitrosoheptamethyleneimine

Our plain-English summary of Hyperplastic and Neoplastic Changes in the Lungs of Rats Treated Concurrently with Chrysotile Asbestos and N-Nitrosoheptamethyleneimine, by P.T. Harrison, J.A. Hoskins, R.C. Brown, et al (Inhalation Toxicology, 2000).

The study

• Authors: P.T. Harrison, J.A. Hoskins, R.C. Brown, G.H. Pigott, P.M. Hext, M.A. Mugglestone
• Journal: Inhalation Toxicology
• Published: 2000;12 Suppl 3:167-72
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This study investigated the combined effect in rat lungs of simultaneous exposure to chrysotile asbestos and N-nitrosoheptamethyleneimine (NHMI), with the objective of determining the potential for chrysotile to promote or otherwise enhance the pathological responses to this potent rodent lung carcinogen. Groups of 15 or 20 male and female animals were treated with 0, 3, or 10 mg kg(-1) NHMI subcutaneously, once a week for 10 wk, plus either clean air (control) or 50 mg m(-3) chrysotile by nose-only inhalation for 4 wk. A broad range of pulmonary metaplastic, hyperplastic, and neoplastic lesions was observed. Effects were more marked in male than in female animals. NHMI treatment increased the incidence of hyperplastic lesions, with apparent augmentation by chrysotile exposure (not statistically significant). Similarly, a "promoting" effect of chrysotile in the induction of lung tumors was observed, with all but 2 of the 11 primary tumors detected being in animals treated with both NHMI and asbestos. However, this apparent interaction was again not confirmable statistically, probably because of the low number of observed tumors (stemming from premature termination of the experiment). The study results are in line with those of similar previous studies, which found a higher incidence of hyperplastic and neoplastic changes in animals treated with both nitrosamine and asbestos than in those given nitrosamine alone. It is proposed that the method described (with minor modification) could be used to investigate either (1) the ability of other inhaled particles to augment NHMI carcinogenicity, or (2) the propensity of other chemical carcinogens to interact with asbestos in the production of pulmonary neoplasms.

In plain English

This rat experiment tested whether inhaled chrysotile asbestos strengthens lung changes caused by N-nitrosoheptamethyleneimine (NHMI), a known rodent lung carcinogen. Groups of 15 (untreated controls) or 20 male and female rats received under-the-skin injections of 0, 3 or 10 mg/kg NHMI weekly for 10 weeks. They also breathed either clean air or about 50 mg per cubic metre of UICC Rhodesian chrysotile, nose-only, for 4 weeks. The rats were examined after 15 months, earlier than planned, because a Kilham virus outbreak forced the experiment to stop. Lung hyperplasia (cell overgrowth) was more common in treated rats than in controls, and some types were more common in males. Of 11 primary lung tumors found, all but 2 were in rats given both NHMI and asbestos. However, the study did not show a statistically significant interaction between NHMI and chrysotile (an extra effect from the two together) for hyperplasia or for tumors. The authors concluded that both agents caused hyperplastic changes. They also concluded that a possible tumor-promoting effect of chrysotile was seen but not confirmed statistically, probably because few tumors developed.

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 (rats given a chemical lung carcinogen by injection, combined with chrysotile asbestos or clean air by inhalation)
• Who was studied: Male and female specific-pathogen-free ALPK:APfSD (Wistar-derived) albino rats from Alderley Park, Cheshire, UK, about 6 weeks old at the start. Each sex was split into six groups: 15 rats per group in the no-treatment control group and 20 in each of the others. The article does not give dates.
• Exposure: NHMI at 0 (vehicle only), 3 or 10 mg/kg was injected subcutaneously once a week for 10 weeks. Rats also had nose-only inhalation, 6 h/day, 5 days/week for 4 weeks, of either clean air or approximately 50 mg per cubic metre of respirable UICC Rhodesian chrysotile asbestos fibers. The target cumulative loading was approximately 6000 mg per cubic metre times hours. Animals were killed after 15 months.
• Main results:
  • Type II cell hyperplasia, alveolar epithelialization, focal bronchioloalveolar-cell hyperplasia and adenomatoid hyperplasia occurred more often in rats treated with NHMI and/or chrysotile than in controls.
  • Of the 11 primary lung tumors detected (adenoma and carcinoma), all but 2 were in rats treated with both NHMI and asbestos.
  • Sex had statistically significant effects on type II cell hyperplasia (P = .03) and focal bronchioloalveolar-cell hyperplasia (P = .02). Both lesions were more common in males than in females.
  • NHMI had statistically significant effects on type II cell hyperplasia (P < .001), focal bronchioloalveolar-cell hyperplasia (P < .001), adenomatoid hyperplasia (P < .001) and adenoma (P = .002).
  • Chrysotile had statistically significant effects on type II cell hyperplasia, alveolar epithelialization, focal bronchioloalveolar-cell hyperplasia and adenomatoid hyperplasia (each P < .001), and on adenocarcinoma (P = .04).
  • The only statistically significant interaction was between sex and chrysotile, for adenomatoid hyperplasia (P = .009). The apparent enhancement of NHMI's hyperplastic effects by chrysotile was not statistically significant.
  • A possible promoting effect of chrysotile on the induction of lung tumors was observed but not confirmed statistically.
• The authors' conclusion: The authors concluded that pulmonary hyperplastic changes were induced by both NHMI and chrysotile, and that males were more susceptible than females. Chrysotile appeared to enhance NHMI's effects, but this interaction was not statistically significant. The authors proposed that the method could be used to study other inhaled particles or other chemical carcinogens.
• Limitations the authors state:
  • The experiment was planned to run until the rats were at least 18 months old. It was stopped at 15 months because of a Kilham virus outbreak in the animal house.
  • Some animals were infected with the virus. The authors considered that this did not compromise the study's objectives.
  • The low number of tumors, due to the early termination, probably prevented statistical confirmation of the apparent interaction.
  • The strong effect of the chrysotile exposure may have prevented detection of an interaction. The authors suggested a lower asbestos dose and a longer experiment.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Neoplasm.

Related studies

• Apparent synergy between chrysotile asbestos and N-nitrosoheptamethyleneimine in the induction of pulmonary tumours in rats — P.T. Harrison, J.C. Heath (1988)
• Apparent synergy in lung carcinogenesis: interactions between N-nitrosoheptamethyleneimine, particulate cadmium and crocidolite asbestos fibres in rats — P.T. Harrison, J.C. Heath (1986)
• Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats — T.D. Tetley, P.M. Hext, et al. (1976)
• Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case — Y. Tsukamoto, T. Otsuki, et al. (2015)
• Changes in lipid ordering of model phospholipid membranes treated with chrysotile and crocidolite asbestos — E.G. Gendek, A.R. Brody (1990)
• Changes in numbers and dimensions of chrysotile asbestos fibers in lungs of rats following short-term exposure — V.L. Roggli, A.R. Brody (1984)

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