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Induction of Lung Cancer by Passive Smoking in an Animal Model System

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Book cover Lung Cancer

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 74))

Abstract

In 1930, a German physician wrote a paper in which he most strongly suggested that smoking of cigarettes is a cause of lung cancer (1). In the same year, Mertens (2) published the results of a study in which he had exposed individual mice to cigarette smoke. He used a compressible rubber bulb to force cigarette smoke into a glass desiccator. Exposures were from 1-4 h daily, for up to 15 mo. Upon histological examination, he observed inflammatory changes in the lungs, although he was quick to point out that large areas of the lungs showed no pathological alterations. Neoplastic lung lesions were found in two animals. In one mouse, multiple small nodules, classified as adenocarcinomas, were considered to have been pre-existing. The second animal showed several small nodules and, in addition, one large adenocarcinoma, mm in diameter, originating in a bronchus and invading the adjacent parenchyma. The author summarized his findings by stating that he had found one bronchial cancer, but that it was doubtful whether it had been caused by tobacco smoke.

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References

  1. Lickint, F. (1930) Tabak und Tabakrauch als aetiologischer Faktor des Carcinoms. Zeitschrift fuer Krebsforschung 30, 349–365.

    Article  Google Scholar 

  2. Mertens, V. E. (1930) Zigarettenrauch eine Ursache des Lungenkrebses? (Eine Anregung). Zeitschrift fuer Krebsforschung 32, 82–91.

    Article  Google Scholar 

  3. Mohr, U. and Reznik, G. (1978) Tobacco Carcinogenesis, in Pathogenesis and Therapy of Lung Cancer (Harris, C. C., ed.), Marcel Dekker, Inc., New York, pp. 263–368.

    Google Scholar 

  4. International Agency for Research on Cancer (IARC) (1986) Biological Data Relevant to the Evaluation of Carcinogenic Risk to Humans. 1. Carcinogenicity Studies in Animals, in IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Tobacco Smoking Vol. 38 (WHO IARC, ed.), IARC, Lyon, pp. 127–139.

    Google Scholar 

  5. Henry, C. J. and Kouri, R. E. (1984) Chronic Exposure of Mice to Cigartte Smoke. Final Report, The Council for Tobacco Research-USA, Inc. Contract CTR-030, “Smoke Inhalation in Mice.” Field, Rich & Associates, New York.

    Google Scholar 

  6. Henry, C. J. and Kouri, R. E. (1986) Chronic inhalation studies in mice. II. Effects of long-term exposure to 2R1 cigarette smoke on (C57BL/Cum × C3H/AnfCum)F1 mice. J. Natl. Cancer Inst. 77, 203–212.

    PubMed  CAS  Google Scholar 

  7. Leuchtenberger, C. and Leuchtenberger, R. (1970) Effects of chronic inhalation of whole fresh cigarette smoke and of its gas phase on pulmonary tumorigenesis in Snell’ s mice, in Morphology of Experimental Respiratory Carcinogenesis. (Nettesheim, P., Hanna, M. G., Jr., and Deatherage, J. W., Jr., eds.) Proceedings of a Biology Division, Oak Ridge National Laboratory, Conference held in Gatlinburg, Tennessee, May 13-16, 1970. US Atomic Energy Commission, Division of Technical Information, Washington, DC, pp. 329–346.

    Google Scholar 

  8. Leuchtenberger, C. and Leuchtenberger, R. (1974) Differential response of Snell’ s and C57 black mice to chronic inhalation of cigarette smoke. Pulmonary carcinogenesis and vascular alterations in lung and heart. Oncology 29, 122–138.

    Article  PubMed  CAS  Google Scholar 

  9. Harris, R. J., Negroni, G., Ludgate, S., Pick, C. R., Chesterman, F. C., and Maidment, B. J. (1974) The incidence of lung tumours in c57bl mice exposed to cigarette smoke: air mixtures for prolonged periods. Int. J. Cancer 14, 130–136.

    Article  PubMed  CAS  Google Scholar 

  10. Finch, G. L., Nikula, K. J., Barr, E. B., Bechtold, W. E., Chen, B. T., Griffith, W. C., et al. (1995) Lung tumor synergism between 239PuO2 and cigarette smoke inhaled by Fisher 344 rats. Toxicologist 15, 47 (Abstract).

    Google Scholar 

  11. Finch, G. L., Nikula, K. J., Belinsky, S. A., Barr, E. B., Stoner, G. D., and Lechner, J. F. (1996) Failure of cigarette smoke to induce or promote lung cancer in the A/J mouse. Cancer Lett. 99, 161–167.

    Article  PubMed  CAS  Google Scholar 

  12. Coggins, C. R. E. (1998) A review of the chronic inhalation studies with mainstream cigarette smoke in rats and mice. Toxicol. Pathol. 26, 307–314.

    Article  PubMed  CAS  Google Scholar 

  13. Hecht, S. S. (1999) Tobacco smoke carcinogens and lung cancer. J. Natl. Cancer Inst. 91, 1194–1210.

    Article  PubMed  CAS  Google Scholar 

  14. Binns, R., Lugton, W. G., and Dyas, B. J. (1978) The effect of exposure conditions on cigarette smoke deposition in the respiratory system of male rats, in Clinical Toxicology (Duncan, W. A. and Leonard, B. J., eds.), Excerpta Medica, Amsterdam, pp. 267–269.

    Google Scholar 

  15. Binns, R., Lugton, W. G., Wilton, L. V., and Dyas, B. J. (1978) Inhalation toxicity studies on cigarette smoke. V. Deposition of smoke particles in the respiratory system of rats under various exposure conditions. Toxicology 9, 87–102.

    Article  PubMed  CAS  Google Scholar 

  16. Witschi, H. P., Oreffo, V. I. C., and Pinkerton, K. E. (1995) Six month exposure of strain A/J mice to cigarette sidestream smoke: cell kinetics and lung tumor data. Fundam. Appl. Toxicol. 26, 32–40.

    Article  PubMed  CAS  Google Scholar 

  17. Witschi, H. P., Espiritu, I., Peake, J. L., Wu, K., Maronpot, R. R., and Pinkerton, K. E. (1997) The carcinogenicity of environmental tobacco smoke. Carcinogenesis 18, 575–586.

    Article  PubMed  CAS  Google Scholar 

  18. Witschi, H. P., Espiritu, I., Maronpot, R. R., Pinkerton, K. E., and Jones, A. D. (1997) The carcinogenic potential of the gas phase of environmental tobacco smoke. Carcinogenesis 18, 2035–2042.

    Article  PubMed  CAS  Google Scholar 

  19. Mauderly, J. L., Bechtold, W. E., Bond, J. A., Brooks, A. L., Chen, B. T., Cuddihy, R. G., Harkema, J. R., Henderson, R. F., Johnson, N. F., and Rithidech, K. (1989) Comparison of 3 methods of exposing rats to cigarette smoke. Exp. Pathol. 37, 194–197.

    PubMed  CAS  Google Scholar 

  20. National Cancer Institute (1999) Health Effects of Exposure to Environmental Tobacco Smoke: The Report of the California Environmental Protection Agency. Smoking and Tobacco Control Monograph No. 10. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, NIH Pub. No. 99-4645, Bethesda MD.

    Google Scholar 

  21. Shimkin, M. B. and Stoner, G. D. (1975) Lung tumors in mice: application to carcinogenesis bioassay. Adv. Cancer Res. 21, 1–58.

    Article  PubMed  CAS  Google Scholar 

  22. Lorenz, E., Stewart, H. L., Daniel, J. H., and Warren, S. (1943) The effects of breathing tobacco smoke on strain A mice. Cancer Res. 3, 123. (Abstract.)

    Google Scholar 

  23. Essenberg, J. M. (1952) Cigarette smoke and the incidence of primary neoplasm of the lung in the albino mouse. Science 116, 561–562.

    Article  PubMed  CAS  Google Scholar 

  24. Essenberg, J. M., Horowitz, M., and Gaffney, E. (1955). The incidence of lung tumors in albino mice exposed to the smoke from cigarettes low in nicotine content. West. J. Surg. Obstet. Gynecol. 63, 265–267.

    PubMed  CAS  Google Scholar 

  25. Essenberg, J. M. (1957) Further study of tumor formation in the lungs of the albino mice. West. J. Surg. Obstet. Gynecol. 65, 161–163.

    PubMed  CAS  Google Scholar 

  26. Adkins, B. J., Van Stee, E. W., Simmons, J. E., and Eustis, S. L. (1986) Oncogenic response of strain A/J mice to inhaled chemicals. J. Toxicol. Environ. Health 17, 311–322.

    Article  PubMed  CAS  Google Scholar 

  27. Pepelko, W. E. and Peirano, W. B. (1983) Health effects of exposure to Diesel exhaust emissions. J. Am. Coll. Toxicol. 2, 253–306.

    Article  CAS  Google Scholar 

  28. Leong, B. K., MacFarland, H. N., and Reese, W. H.,Jr. (1971) Induction of lung adenomas by chronic inhalation of bis (chloromethyl) ether. Arch. Environ. Health 22, 663–666.

    PubMed  CAS  Google Scholar 

  29. Witschi, H., Espiritu, I., Pinkerton, K. E., Murphy, K., and Maronpot, R. (1999) Ozone Carcinogenesis Revisited. Toxicol. Sci. 52, 162–167.

    Article  PubMed  CAS  Google Scholar 

  30. Boorman, G. A., Sills, R. C., Grumbein, S., Hailey, R., Miller, R. A., and Herbert, R. A. (1995) Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice. Toxicol. Lett. 8283, 301–306.

    Article  PubMed  Google Scholar 

  31. Stoner, G. D. and Shimkin, M. B. (1985) Lung tumors in strain A mice as a bioassay for carcinogenicity, in Handbook of Carcinogen Testing (Milman, H. and Weisburger, E. K., eds.), Noyes Publications, Park Ridge, NJ, pp. 179–214.

    Google Scholar 

  32. Hammond, E. C. (1966) Smoking in relation to the death rates of one million men and women. Natl. Cancer Inst. Monogr. 19, 127–204.

    PubMed  CAS  Google Scholar 

  33. Wynder, E. L. and Stellman, S. D. (1977) Comparative epidemiology of tobacco-related cancers. Cancer Res. 37, 4608–4622.

    PubMed  CAS  Google Scholar 

  34. Postmus, P. E. (1998) Epidemiology of lung cancer, in Fishman’ s Pulmonary Diseases and Disorders (Fishman, A. P., Elias, J. A., Fishman, J. A., Grippi, M. A., Kaiser, L. R., and Senior, R. M., eds.), McGraw-Hill, New York, pp. 1707–1717.

    Google Scholar 

  35. Witschi, H., Espiritu, I., and Uyeminami, D. (1999) Chemoprevention of tobacco smoke-induced lung tumors in A/J strain mice with dietary myo-inositol and dexamethasone. Carcinogenesis 20, 1375–1378.

    Article  PubMed  CAS  Google Scholar 

  36. Witschi, H., Uyeminami, D., Moran, D., and Espiritu, I. (2000) Chemoprevention of tobacco-smoke lung carcinogenesis in mice after cessation of smoke exposure. Carcinogenesis 21, 977–982.

    Article  PubMed  CAS  Google Scholar 

  37. Teague, S. V., Pinkerton, K. E., Goldsmith, M., Gebremichael, A., Chang, S., Jenkins, R. A., and Moneyhun, J. H. (1994) Sidestream cigarette smoke generation and exposure system for environmental tobacco smoke studies. Inhal. Toxicol. 6, 79–93.

    Article  CAS  Google Scholar 

  38. Wong, B. A. (1999) Inhalation systems design, methods and operation, in Toxicology of the Lung (Gardner, D. E., Crapo, J. D., and McClellan, R. O., eds.), Taylor & Francis, Philadelphia, PA, pp. 1–53.

    Google Scholar 

  39. Hext, P. M. (1999) Inhalation Toxicology, in General and Applied Toxicology (Ballantyne, B., Marrs, T. C., and Syversen, T., eds.), Grove’ s Dictionaries, Inc., New York, pp. 587–602.

    Google Scholar 

  40. Kennnedy, G. L. and Valentine, R. (1994) Inhalation Toxicology, in Principles and Methods of Toxicology (Hayes, A. W., ed.), Raven Press, New York, pp. 805–838.

    Google Scholar 

  41. Dontenwill, W. (1970) Experimental investigations on the effect of cigarette smoke inhalation on small laboratory animals, in Morphology of Experimental Respiratory Carcinogenesis (Nettesheim, P., Hanna, M. G., Jr., and Deatherage, J. W., Jr., eds.), Proceedings of a Biology Division, Oak Ridge National Laboratory, conference held in Gatlinburg, Tennessee, May 13–16, 1970. U.S. Atomic Energy Commission, Division of Technical Journals, Washington, DC, pp. 389–412.

    Google Scholar 

  42. Baumgartner, H. and Coggins, C. R. (1980) Description of a continuous-smoking inhalation machine for exposing small animals to tobacco smoke. Beitr. Tabakforsch. Int. 10, 169–174.

    Google Scholar 

  43. Guerin, M. R., Jenkins, R. A., and Tomkins, B. A. (1992) The Chemistry of Environmental Tobacco Smoke: Composition and Measurement. Indoor Air Research Series. Lewis Publishers, Boca Raton, FL.

    Google Scholar 

  44. Ayres, P. H., Mosberg, A. T., and Coggins, C. R. (1994) Design, construction, and evaluation of an inhalation system for exposing experimental animals to environmental tobacco smoke. Am. Ind. Hyg. Assoc. J. 55, 806–810.

    Article  PubMed  CAS  Google Scholar 

  45. Coggins, C. R., Ayres, P. H., Mosberg, A. T., Ogden, M. W., Sagartz, J. W., and Hayes, A. W. (1992) Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette. I. Inhalation toxicology and histopathology. Fundam. Appl. Toxicol. 19, 133–140.

    Article  PubMed  CAS  Google Scholar 

  46. Lee, C. K., Brown, B. G., Reed, E. A., Coggins, C. R., Doolittle, D. J., and Hayes, A. W. (1993) Ninety-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette: DNA adducts and alveolar macrophage cytogenetics. Fundam. Appl. Toxicol. 20, 393–401.

    Article  PubMed  CAS  Google Scholar 

  47. Haussmann, H. J., Anskeit, E., Becker, D., Kuhl, P., Stinn, W., Teredesai, A., et al. (1998) Comparison of fresh and room-aged cigarette sidestream smoke in a subchronic inhalation study on rats. Toxicol. Sci. 41, 100–116.

    Article  PubMed  CAS  Google Scholar 

  48. Haussmann, H. J., Gerstenberg, B., Goecke, W., Kuhl, P., Schepers, G., Stabbert, R., et al. (1998) 12-Month inhalation study on room-aged cigarette sidestream smoke in rats. Inhal. Toxicol. 10, 663–697.

    Article  CAS  Google Scholar 

  49. Griffith, R. B. (1984) A simple machine for smoke analytical studies and total particulate matter collection for biological studies. Toxicology 33, 33–41.

    Article  PubMed  CAS  Google Scholar 

  50. Griffith, R. B. and Hancock, R. (1985) Simultaneous mainstream-sidestream smoke exposure systems I. Equipment and procedures. Toxicology 34, 123–138.

    Article  PubMed  CAS  Google Scholar 

  51. Griffith, R. B. and Standafer, S. (1985) Simultaneous mainstream-sidestream smoke exposure systems II. The rat exposure system. Toxicology 35, 13–24.

    Article  PubMed  CAS  Google Scholar 

  52. Witschi, H. P. (1981) Enhancement of tumor formation in mouse lung by dietary butylated hydroxytoluene. Toxicology 21, 95–104.

    Article  PubMed  CAS  Google Scholar 

  53. Maronpot, R. R., Shimkin, M. B., Witschi, H. P., Smith, L. H., and Cline, J. M. (1986) Strain A mouse pulmonary tumor test results for chemicals previously tested in the National Cancer Institute carcinogenicity tests. J. Natl. Cancer Inst. 76, 1101–1112.

    PubMed  CAS  Google Scholar 

  54. Maronpot, R. R. (1991) Correlation of data from the strain A mouse bioassay with long-term bioassays. Exp. Lung Res. 17, 425–431.

    Article  PubMed  CAS  Google Scholar 

  55. Witschi, H., Espiritu, I., Yu, M., and Willits, N. H. (1998) The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice. Carcinogenesis 19, 1789–1794.

    Article  PubMed  CAS  Google Scholar 

  56. Witschi, H. (2000) Successful and not so successful chemoprevention of tobacco smoke-induced lung tumors. Exp. Lung Res. 26, 743–756.

    Article  PubMed  CAS  Google Scholar 

  57. John, L. C. H. (2001) Assessment of murine lung tumour development: a comparison of two techniques. Br. J. Biomed. Sciences 58, 159–163.

    CAS  Google Scholar 

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Witschi, H. (2003). Induction of Lung Cancer by Passive Smoking in an Animal Model System. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicine™, vol 74. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-323-2:441

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  • DOI: https://doi.org/10.1385/1-59259-323-2:441

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-985-8

  • Online ISBN: 978-1-59259-323-1

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