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. 1984 Jun;56:75–86. doi: 10.1289/ehp.845675

Heterotopic tracheal transplants: techniques and applications.

A J Klein-Szanto, B C Pal, M Terzaghi, A C Marchok
PMCID: PMC1568199  PMID: 6383803

Abstract

Heterotopic tracheal transplants, placed subcutaneously in syngeneic rats have been extensively used in our laboratory. The objective of these experiments was to study the toxic and/or carcinogenic effect of several compounds on the respiratory tract mucosa. This was attained by exposing the transplants to an intraluminal pettet containing the toxicant or carcinogen mixed with an adequate matrix (gelatin, beeswax, stearyl alcohol, silastic, etc.). By varying the concentration of the test chemicals, it is possible to study dose-response relationships, and by changing the pellet matrix, the effects of release rate (dose rate) can be analyzed. Several end points can be studied, such as histological changes in the mucociliary epithelium, changes in mucus secretion, tumor induction and changes in the in vitro behavior of the epithelial cells after in vivo exposure. In addition, by de-epithelializing the tracheal transplants and reseeding them with another cell population, e.g., from previously treated cell cultures or from human specimens and transplanting them subcutaneously in nude mice, completely new vistas on the effect of chemicals can be opened.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boutwell R. K. The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol. 1974 Jan;2(4):419–443. doi: 10.3109/10408447309025704. [DOI] [PubMed] [Google Scholar]
  2. Clark J. N., Klein-Szanto A. J., Pine A. H., Stephenson K. B., Marchok A. C. Reestablishment of a mucociliary epithelium in tracheal organ cultures exposed to retinyl acetate: a biochemical and morphometric study. Eur J Cell Biol. 1980 Aug;21(3):261–268. [PubMed] [Google Scholar]
  3. Clark J. N., Marchok A. C. Characterization of mucin isolated from rat tracheal transplants. Biochim Biophys Acta. 1979 Dec 11;588(3):357–367. doi: 10.1016/0304-4165(79)90344-1. [DOI] [PubMed] [Google Scholar]
  4. Craighead J. E., Mossman B. T. Carcinoma induction by 3-methylcholanthrene in hamster tracheal tissue implanted in syngeneic animals. Prog Exp Tumor Res. 1979;24:48–60. doi: 10.1159/000402083. [DOI] [PubMed] [Google Scholar]
  5. DONTENWILL W. EXPERIMENTELLE UNTERSUCHUNGEN ZUR GENESE DES LUNGENCARCINOMS. Arzneimittelforschung. 1964 Jul;14:774–780. [PubMed] [Google Scholar]
  6. Ebenstein P., Kinder B., Bankole D. O., Richards F. F., Armstrong M. Y. Expression of endogenous xenotropic retrovirus by methylcholanthrene-induced squamous cell carcinoma of the mouse respiratory tract. J Exp Med. 1979 Dec 1;150(6):1567–1570. doi: 10.1084/jem.150.6.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Griesemer R. A., Nettesheim P., Martin D. H., Caton J. E., Jr Quantitative exposure of grafted rat tracheas to 7, 12-dimethylbenz(a)anthracene. Cancer Res. 1977 May;37(5):1266–1271. [PubMed] [Google Scholar]
  8. HIGUCHI T. MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. J Pharm Sci. 1963 Dec;52:1145–1149. doi: 10.1002/jps.2600521210. [DOI] [PubMed] [Google Scholar]
  9. KNUDTSON K. P. A method of study of squamous metaplasia, atypical change, and early bronchogenic carcinoma of the bronchial mucosa in smokers and nonsmokers. Cancer. 1956 Jan-Feb;9(1):84–85. doi: 10.1002/1097-0142(195601/02)9:1<84::aid-cncr2820090107>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  10. Kendrick J., Nettesheim P., Hammons A. S. Tumor induction in tracheal grafts: a new experimental model for respiratory carcinogenesis studies. J Natl Cancer Inst. 1974 Apr;52(4):1317–1325. doi: 10.1093/jnci/52.4.1317. [DOI] [PubMed] [Google Scholar]
  11. Klein-Szanto A. J., Nettesheim P., Pine A., Martin D. Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium. Am J Pathol. 1981 May;103(2):263–270. [PMC free article] [PubMed] [Google Scholar]
  12. Klein-Szanto A. J., Nettesheim P., Topping D. C., Olson A. C. Quantitative analysis of disturbed cell maturation in dysplastic lesions of the respiratory tract epithelium. Carcinogenesis. 1980;1(12):1007–1016. doi: 10.1093/carcin/1.12.1007. [DOI] [PubMed] [Google Scholar]
  13. Klein-Szanto A. J., Topping D. C., Heckman C. A., Nettesheim P. Ultrastructural characteristics of carcinogen-induced dysplastic changes in tracheal epithelium. Am J Pathol. 1980 Jan;98(1):83–100. [PMC free article] [PubMed] [Google Scholar]
  14. Klein-Szanto A. J., Topping D. C., Heckman C. A., Nettesheim P. Ultrastructural characteristics of carcinogen-induced nondysplastic changes in tracheal epithelium. Am J Pathol. 1980 Jan;98(1):61–82. [PMC free article] [PubMed] [Google Scholar]
  15. Kobayashi N., Kanisawa M., Okamoto T., Okita M., Katsuki H. Sequential cytologic study of the development of squamous cell carcinoma induced in subcutaneously implanted bronchial autograft of dog. Acta Cytol. 1978 Mar-Apr;22(2):99–104. [PubMed] [Google Scholar]
  16. Kobayashi N., Okamoto T., Yarita T., Tanaka K., Okita M. Cancer induction in subcutaneously implanted bronchial autograft of a dog by 3-methylcholanthrene. Gan. 1976 Aug;67(4):611–615. [PubMed] [Google Scholar]
  17. Lane B. P., Mass M. J. Carcinogenicity and cocarcinogenicity of chromium carbonyl in heterotopic tracheal grafts. Cancer Res. 1977 May;37(5):1476–1479. [PubMed] [Google Scholar]
  18. Marchok A. C., Clark J. N., Klein-Szanto A. Modulation of growth, differentiation, and mucous glycoprotein synthesis by retinyl acetate in cloned carcinoma cell lines. J Natl Cancer Inst. 1981 Jun;66(6):1165–1174. [PubMed] [Google Scholar]
  19. Marchok A. C., Rhoton J. C., Nettesheim P. In vitro development of oncogenicity in cell lines established from tracheal epithelium preexposed in vivo to 7,12-dimethylbenz(a)anthracene. Cancer Res. 1978 Jul;38(7):2030–2037. [PubMed] [Google Scholar]
  20. Mossman B. T., Craighead J. E. Induction of neoplasms in hamster tracheal grafts with 3-methylcholanthrene-coated Lycra fibers. Cancer Res. 1978 Nov;38(11 Pt 1):3717–3722. [PubMed] [Google Scholar]
  21. Nettesheim P., Griesemer R. A., Martin D. H., Caton J. E., Jr Induction of preneoplastic and neoplastic lesions in grafted rat tracheas continuously exposed to benzo(a)pyrene. Cancer Res. 1977 May;37(5):1272–1278. [PubMed] [Google Scholar]
  22. Nettesheim P., Klein-Szanto A. J., Marchok A. C., Steele V. E., Terzaghi M., Topping D. C. Studies of neoplastic development in respiratory tract epithelium. Arch Pathol Lab Med. 1981 Jan;105(1):1–10. [PubMed] [Google Scholar]
  23. Pal B. C., Topping D. C., Griesemer R. A., Nelson F. R., Nettesheim P. Development of a system for controlled release of benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, and phorbol ester for tumor induction in heterotopic tracheal grafts. Cancer Res. 1978 May;38(5):1376–1383. [PubMed] [Google Scholar]
  24. SMITH W. E. The tissue transplant technic as a means of testing materials for carcinogenic action. Cancer Res. 1949 Dec;9(12):712-23, illust. [PubMed] [Google Scholar]
  25. Shors E. C., Fu P. C., Matsumura K., Cohen A. H., Benfield J. R. Sustained release of benzo(a)pyrene from silicone polymer into the tracheobronchial tree of hamsters and dogs. Cancer Res. 1980 Jul;40(7):2288–2294. [PubMed] [Google Scholar]
  26. Smith L. L., Smart V. B., Ansari G. A. Mutagenic cholesterol preparations. Mutat Res. 1979 Sep;68(1):23–30. doi: 10.1016/0165-1218(79)90074-0. [DOI] [PubMed] [Google Scholar]
  27. Smith W. E., Yazdi E., Miller L. Carcinogenesis in pulmonary epithelia in mice on different levels of vitamin A. Environ Res. 1972 Jun;5(2):152–163. doi: 10.1016/0013-9351(72)90030-8. [DOI] [PubMed] [Google Scholar]
  28. Terzaghi M., Klein-Szanto A. J. Differentiation of normal and cultured preneoplastic tracheal epithelial cells in rats: importance of epithelial mesenchymal interactions. J Natl Cancer Inst. 1980 Nov;65(5):1039–1048. [PubMed] [Google Scholar]
  29. Terzaghi M., Nettesheim P. Dynamics of neoplastic development in carcinogen-exposed tracheal mucosa. Cancer Res. 1979 Oct;39(10):4003–4010. [PubMed] [Google Scholar]
  30. Terzaghi M., Nettesheim P., Riester L. Effect of carcinogen dose on the dynamics of neoplastic development in rat tracheal epithelium. Cancer Res. 1982 Nov;42(11):4511–4518. [PubMed] [Google Scholar]
  31. Terzaghi M., Nettesheim P., Williams M. L. Repopulation of denuded tracheal grafts with normal, preneoplastic, and neoplastic epithelial cell populations. Cancer Res. 1978 Dec;38(12):4546–4553. [PubMed] [Google Scholar]
  32. Topping D. C., Griesemer R. A., Nettesheim P. Quantitative assessment of generalized epithelial changes in tracheal mucosa following exposure to 7,12-dimethylbenz(a)anthracene. Cancer Res. 1979 Dec;39(12):4823–4828. [PubMed] [Google Scholar]
  33. Topping D. C., Nettesheim P., Martin D. H. Toxic and tumorigenic effects of asbestos on tracheal mucosa. J Environ Pathol Toxicol. 1980 Jun-Jul;3(5-6):261–275. [PubMed] [Google Scholar]
  34. Topping D. C., Nettesheim P. Promotion-like enhancement of tracheal carcinogenesis in rats by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1980 Dec;40(12):4352–4355. [PubMed] [Google Scholar]
  35. Topping D. C., Nettesheim P. Two-stage carcinogenesis studies with asbestos in Fischer 344 rats. J Natl Cancer Inst. 1980 Sep;65(3):627–630. [PubMed] [Google Scholar]
  36. Topping D. C., Pal B. C., Martin D. H., Nelson F. R., Nettesheim P. Pathologic changes induced in respiratory tract mucosa by polycyclic hydrocarbons of differing carcinogenic activity. Am J Pathol. 1978 Nov;93(2):311–324. [PMC free article] [PubMed] [Google Scholar]
  37. Watt J., Gregory I., Stell P. M. A simple method for the post-mortem demonstration of squamous metaplasia in the larynx. J Pathol. 1971 Jun;104(2):149–151. doi: 10.1002/path.1711040210. [DOI] [PubMed] [Google Scholar]
  38. Watt J., Gregory I., Stell P. M. An alcian blue-phloxine method for the gross demonstration of squamous metaplasia in the larynx. J Pathol. 1975 May;116(1):31–36. doi: 10.1002/path.1711160105. [DOI] [PubMed] [Google Scholar]
  39. Yarita T., Nettesheim P. Carcinogenicity of nickel subsulfide for respiratory tract mucosa. Cancer Res. 1978 Oct;38(10):3140–3145. [PubMed] [Google Scholar]

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