ANIMAL MODEL OF HUMAN DISEASE
Carcinoma of the Larvnx in Hamsters Exposed to Cigarette Smoke
Animal Model: Susceptible Inbred Line of Syrian Hamsters (BIO 13.16) Contributed by: F. Homburger, MD, Henry Soto, MD, Bio-Research Institute, Cambridge, Massachusetts, and Department of Pathology, Boston University School of Medicine; J. Althoff, MD, Medizinische Hochschule, Hannover, Germany; P. Dalquen, MD, and P. Heitz, MD, Institute for Pathology, University of Basel, Switzerland. Biolog Characteristics
Laryngeal changes (including cancer in fewer than 10% of the exposed animals) were first induced by cigarette smoke by Dontenwill ' in randombred Syrian hamsters. Using a susceptible inbred line of Sy/rian hamsters (BIO 13.16), Bernfeld et al induced laryngeal carcinoma in as many as 47%% of the animals exposed to cigarette smoke for more than 53 weeks. The methods employed and the changes observed have been published.2 5,12 Comparison With Humans
Ty-pical instances of epithelial changes leading to carcinoma observed in smoke-exposed Syrian hamsters are illustrated in the even numbered photographs. The odd numbered photomicrographs were selected from laryngeal biopsies obtained from heavy smokers at the Universitv Hospital in Basel, Switzerland, to match the histologic changes observed in the experimental animals. The morphologic resemblance between these two sets of observations is striking. From the light microscopic point of view, cancer of the larynx induced by cigarette smoking in hamsters is indistinguishable from cancer of the larvnx in humans. The same precancerous stages may be discerned in the lesions from both species. Cancer of the larvnx is unknown in untreated hamsters.6 Association Wrth Smoking and Alcohol Consumption
Epidemiologic studies show that cancer of the larvnx is closelv associated with smoking and alcohol consumption.7'8 Smokers over 63 vears of Publication sponsored by the Registrv of Comparatise Pathology of the Armed Forces Institute of and supported b%- Public Health Senice Grant RR 010833 from the Division of Research Resources. U S Department of Health. Education and W\eifare. under the auspices of Universities Associated for Research and Education in Pathology. Inc
Pathology
0002-9440/79/0607-0845$01.00
© 1979 American Association of Pathologists
845
846
HOMBURGER ET AL
American Journal of Pathology
age have a nine times greater risk of developing cancer of the larynx than do nonsmokers (for cancer of the lung the comparative figure is 11.6).1 In the Danish capital the morbidity from larynx cancer has risen from 2.2 in 10,000 during the period from 1943 to 1947 to 9.6 in 10,000 for the period from 1968 to 1972.10 In Thailand, recently, carcinoma of the larynx accounted for 18% of all histologically diagnosed cancers.1" This well-defined neoplastic disease of humans has now been reproduced in certain susceptible inbred Syrian hamsters by exposing them to cigarette smoke inhalation. We may safely assume that the same etiology operates in humans. Controlled experimental studies on alcohol as a cocarcinogen are now feasible. Availability
The source of cigarette-smoke-susceptible inbred BIO 15.16- hamsters was TELACO, Bar Harbor, Maine, a subsidiary of Bio-Research Consultants, Inc., 9 Commercial Avenue, Cambridge, MA 02141. References 1. Dontenwill W, Chevalier H-J, Harke H-P, Lafrenz U, Reckzeh G, Schneider B: Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters. J Natl Cancer Inst 51: 1781-1832, 1973 2. Bernfeld P, Homburger F, Russfield AB: Strain differences in the response of inbred Syrian hamsters to cigarette smoke inhalation. J Natl Cancer Inst 53:11411158, 1974
3. Homburger F: "Smokers' larynx" and carcinoma of the larynx in Syrian hamsters exposed to cigarette smoke. The Laryngoscope 85:1874-1881, 1975 4. Bernfeld P, Homburger F: Cigarette smoke inhalation studies in inbred Syrian hamsters: I. Method and dosimetry. Abstract 156, Society of Toxicology Meeting, San Francisco, 1978 5. Homburger F, Pai KJ, Soto E, Bernfeld P: Cigarette smoke inhalation studies in inbred Syrian hamsters: II. Histopathological lesions in the respiratory tract: Abstract 157, Society of Toxicology Meeting, San Francisco, 1978 6. Pour P, Mohr U, Cardesa A, Althoff J, Kmoch N: Spontaneous tumors and common diseases in two colonies of Syrian hamsters: II. Respiratory tract and digestive system. J Natl Cancer Inst 56:937-948, 1976 7. Blot WJ, Fraumeni FJ Jr, Morris LE: Patterns of laryngeal cancer in the United States. Lancet 2 (8091):674-675, 1978 8. Wynder EL, Bross IJ, Day S: A study of environmental factors in cancer of the larynx. Cancer 9:86-110, 1956 9. Hammond EC: Tobacco, Persons at High Risk of Cancer: An Approach to Cancer Etiology and Control. Edited by JF Fraumeni Jr. New York, Academic Press, 1975, p 133 10. Clemmensen J: Statistical studies in malignant neoplasms. V. Trends and risks, Denmark 1943-72. Acta Pathol Microbiol Scand [A] Suppl 261: 1-139, 1977 11. Simarak S, De Jong UW, Breslow N, Dahl CJ, Ruchphaopunt K, Scheelings P, Maclennen R, et al: Cancer of the oral cavity, pharynx/larynx and lung in North Thailand: case-control study and analysis of cigar smoke. Br J Cancer 36:130-140, 1977 12. Bernfeld P, Homburger F, Soto E, Pai KJ: Cigarette smoke inhalation studies in inbred Syrian hamsters. J Natl Cancer Inst (In press)
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Figure 2-Normal respiratory epitheFiure 1-Human normal respiratory epithelium. (H&E, x 100) lium of old, cage-held control hamster. Figure 3-Human squamous cell metaplasia of respiratory epithelium. (H&E, x 64) F4iure 4-Squamous cell metaplasia of respiratory epithelium of hamster. Figure 6-Hamster squamous Fure 5-Human squamous cell metaplasia. (H&E, x 125) (x 125) cell metaplasia.
Figure 7-Human papilloma of larynx. (H&E) Figure 8-Hamster papilloma of larynx. (X 125) Figure 9-Human highly differentiated squamous cell carcinoma. (H&E, x 64) Figure 10-Differentiated squamous cell carcinoma of 92-week-old hamster. Figure 11-Human poorly differentiated squamous cell carcinoma. (H&E, x 64) Figure 12-Poorly differentiated carcinoma in 91-week-old hamster.
Carcinoma of the Larvnx in Hamsters Exposed to Cigarette Smoke
Animal Model: Susceptible Inbred Line of Syrian Hamsters (BIO 13.16) Contributed by: F. Homburger, MD, Henry Soto, MD, Bio-Research Institute, Cambridge, Massachusetts, and Department of Pathology, Boston University School of Medicine; J. Althoff, MD, Medizinische Hochschule, Hannover, Germany; P. Dalquen, MD, and P. Heitz, MD, Institute for Pathology, University of Basel, Switzerland. Biolog Characteristics
Laryngeal changes (including cancer in fewer than 10% of the exposed animals) were first induced by cigarette smoke by Dontenwill ' in randombred Syrian hamsters. Using a susceptible inbred line of Sy/rian hamsters (BIO 13.16), Bernfeld et al induced laryngeal carcinoma in as many as 47%% of the animals exposed to cigarette smoke for more than 53 weeks. The methods employed and the changes observed have been published.2 5,12 Comparison With Humans
Ty-pical instances of epithelial changes leading to carcinoma observed in smoke-exposed Syrian hamsters are illustrated in the even numbered photographs. The odd numbered photomicrographs were selected from laryngeal biopsies obtained from heavy smokers at the Universitv Hospital in Basel, Switzerland, to match the histologic changes observed in the experimental animals. The morphologic resemblance between these two sets of observations is striking. From the light microscopic point of view, cancer of the larynx induced by cigarette smoking in hamsters is indistinguishable from cancer of the larvnx in humans. The same precancerous stages may be discerned in the lesions from both species. Cancer of the larvnx is unknown in untreated hamsters.6 Association Wrth Smoking and Alcohol Consumption
Epidemiologic studies show that cancer of the larvnx is closelv associated with smoking and alcohol consumption.7'8 Smokers over 63 vears of Publication sponsored by the Registrv of Comparatise Pathology of the Armed Forces Institute of and supported b%- Public Health Senice Grant RR 010833 from the Division of Research Resources. U S Department of Health. Education and W\eifare. under the auspices of Universities Associated for Research and Education in Pathology. Inc
Pathology
0002-9440/79/0607-0845$01.00
© 1979 American Association of Pathologists
845
846
HOMBURGER ET AL
American Journal of Pathology
age have a nine times greater risk of developing cancer of the larynx than do nonsmokers (for cancer of the lung the comparative figure is 11.6).1 In the Danish capital the morbidity from larynx cancer has risen from 2.2 in 10,000 during the period from 1943 to 1947 to 9.6 in 10,000 for the period from 1968 to 1972.10 In Thailand, recently, carcinoma of the larynx accounted for 18% of all histologically diagnosed cancers.1" This well-defined neoplastic disease of humans has now been reproduced in certain susceptible inbred Syrian hamsters by exposing them to cigarette smoke inhalation. We may safely assume that the same etiology operates in humans. Controlled experimental studies on alcohol as a cocarcinogen are now feasible. Availability
The source of cigarette-smoke-susceptible inbred BIO 15.16- hamsters was TELACO, Bar Harbor, Maine, a subsidiary of Bio-Research Consultants, Inc., 9 Commercial Avenue, Cambridge, MA 02141. References 1. Dontenwill W, Chevalier H-J, Harke H-P, Lafrenz U, Reckzeh G, Schneider B: Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters. J Natl Cancer Inst 51: 1781-1832, 1973 2. Bernfeld P, Homburger F, Russfield AB: Strain differences in the response of inbred Syrian hamsters to cigarette smoke inhalation. J Natl Cancer Inst 53:11411158, 1974
3. Homburger F: "Smokers' larynx" and carcinoma of the larynx in Syrian hamsters exposed to cigarette smoke. The Laryngoscope 85:1874-1881, 1975 4. Bernfeld P, Homburger F: Cigarette smoke inhalation studies in inbred Syrian hamsters: I. Method and dosimetry. Abstract 156, Society of Toxicology Meeting, San Francisco, 1978 5. Homburger F, Pai KJ, Soto E, Bernfeld P: Cigarette smoke inhalation studies in inbred Syrian hamsters: II. Histopathological lesions in the respiratory tract: Abstract 157, Society of Toxicology Meeting, San Francisco, 1978 6. Pour P, Mohr U, Cardesa A, Althoff J, Kmoch N: Spontaneous tumors and common diseases in two colonies of Syrian hamsters: II. Respiratory tract and digestive system. J Natl Cancer Inst 56:937-948, 1976 7. Blot WJ, Fraumeni FJ Jr, Morris LE: Patterns of laryngeal cancer in the United States. Lancet 2 (8091):674-675, 1978 8. Wynder EL, Bross IJ, Day S: A study of environmental factors in cancer of the larynx. Cancer 9:86-110, 1956 9. Hammond EC: Tobacco, Persons at High Risk of Cancer: An Approach to Cancer Etiology and Control. Edited by JF Fraumeni Jr. New York, Academic Press, 1975, p 133 10. Clemmensen J: Statistical studies in malignant neoplasms. V. Trends and risks, Denmark 1943-72. Acta Pathol Microbiol Scand [A] Suppl 261: 1-139, 1977 11. Simarak S, De Jong UW, Breslow N, Dahl CJ, Ruchphaopunt K, Scheelings P, Maclennen R, et al: Cancer of the oral cavity, pharynx/larynx and lung in North Thailand: case-control study and analysis of cigar smoke. Br J Cancer 36:130-140, 1977 12. Bernfeld P, Homburger F, Soto E, Pai KJ: Cigarette smoke inhalation studies in inbred Syrian hamsters. J Natl Cancer Inst (In press)
v
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'-
#~WD ~
..}£>v_
2>
e#
±
. z
, *R~~~~vu.
p~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~i
't
.1)
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-t2 .
s
' Ow
Figure 2-Normal respiratory epitheFiure 1-Human normal respiratory epithelium. (H&E, x 100) lium of old, cage-held control hamster. Figure 3-Human squamous cell metaplasia of respiratory epithelium. (H&E, x 64) F4iure 4-Squamous cell metaplasia of respiratory epithelium of hamster. Figure 6-Hamster squamous Fure 5-Human squamous cell metaplasia. (H&E, x 125) (x 125) cell metaplasia.
Figure 7-Human papilloma of larynx. (H&E) Figure 8-Hamster papilloma of larynx. (X 125) Figure 9-Human highly differentiated squamous cell carcinoma. (H&E, x 64) Figure 10-Differentiated squamous cell carcinoma of 92-week-old hamster. Figure 11-Human poorly differentiated squamous cell carcinoma. (H&E, x 64) Figure 12-Poorly differentiated carcinoma in 91-week-old hamster.
