Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1984 Jun;56:61–74. doi: 10.1289/ehp.845661

Biochemical studies of the tracheobronchial epithelium.

M J Mass, D G Kaufman
PMCID: PMC1568211  PMID: 6207017

Abstract

Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. In brief, formidable strides have been made in biochemistry specific to this important target tissue, despite the inability to acquire tracheobronchial epithelium in large quantities.

Full text

PDF
61

Selected References

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

  1. Autrup H., Essigmann J. M., Croy R. G., Trump B. F., Wogan G. N., Harris C. C. Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon. Cancer Res. 1979 Mar;39(3):694–698. [PubMed] [Google Scholar]
  2. Autrup H., Harris C. C., Stoner G. D., Selkirk J. K., Schafer P. W., Trump B. F. Metabolism of [3H]benzo[a]pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages. Lab Invest. 1978 Mar;38(3):217–224. [PubMed] [Google Scholar]
  3. Autrup H., Harris C. C., Trump B. F., Jeffrey A. M. Metabolism of benzo(a)pyrene and identification of the major benzo(a)pyrene-DNA adducts in cultured human colon. Cancer Res. 1978 Nov;38(11 Pt 1):3689–3696. [PubMed] [Google Scholar]
  4. Autrup H., Wefald F. C., Jeffrey A. M., Tate H., Schwartz R. D., Trump B. F., Harris C. C. Metabolism of benzo[a]pyrene by cultured tracheobronchial tissues from mice, rats, hamsters, bovines and humans. Int J Cancer. 1980 Feb 15;25(2):293–300. doi: 10.1002/ijc.2910250219. [DOI] [PubMed] [Google Scholar]
  5. Baseman J. B., Hayes N. S., Goldman W. E., Collier A. M. Mucus and surfactant synthesis and secretion by cultured hamster respiratory cells. Environ Health Perspect. 1980 Apr;35:139–146. doi: 10.1289/ehp.8035139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bjelke E. Dietary vitamin A and human lung cancer. Int J Cancer. 1975 Apr 15;15(4):561–565. doi: 10.1002/ijc.2910150405. [DOI] [PubMed] [Google Scholar]
  7. Bonanni F., De Luca L. Vitamin A-dependent fucose-glycopeptide from rat tracheal epithelium. Biochim Biophys Acta. 1974 May 24;343(3):632–637. doi: 10.1016/0304-4165(74)90282-7. [DOI] [PubMed] [Google Scholar]
  8. Bonanní F., Levinson S. S., Wolf G., De Luca L. Glycoproteins from the hamster respiratory tract and their response to vitamin A. Biochim Biophys Acta. 1973 Feb 28;297(2):441–451. doi: 10.1016/0304-4165(73)90091-3. [DOI] [PubMed] [Google Scholar]
  9. Clamon G. H., Sporn M. B., Smith J. M., Saffiotti U. Alpha- and beta-retinyl acetate reverse metaplasias of vitamin A deficiency in hamster trachea in organ culture. Nature. 1974 Jul 5;250(461):64–66. doi: 10.1038/250064a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Clark J. N., Marchok A. C. The effect of vitamin A on cellular differentiation and mucous glycoprotein synthesis in long-term rat tracheal organ cultures. Differentiation. 1979;14(3):175–183. doi: 10.1111/j.1432-0436.1979.tb01026.x. [DOI] [PubMed] [Google Scholar]
  13. Cohen G. M., Haws S. M., Moore B. P., Bridges J. W. Benzo(a)pyren-3-yl hydrogen sulphate, a major ethyl acetate-extractable metabolite of benzo(a)pyrene in human, hamster and rat lung cultures. Biochem Pharmacol. 1976 Dec 1;25(23):2561–2570. doi: 10.1016/0006-2952(76)90510-4. [DOI] [PubMed] [Google Scholar]
  14. Cohen G. M., Marchok A. C., Nettesheim P., Steele V. E., Nelson F., Huang S., Selkirk J. K. Comparative metabolism of benzo(a)pyrene in organ and cell cultures derived from rat tracheas. Cancer Res. 1979 Jun;39(6 Pt 1):1980–1984. [PubMed] [Google Scholar]
  15. Cohen G. M., Moore B. P. Metabolism of (3H)benzo(a)pyrene by different portions of the respiratory tract. Biochem Pharmacol. 1976 Jul 15;25(14):1623–1629. doi: 10.1016/0006-2952(76)90474-3. [DOI] [PubMed] [Google Scholar]
  16. Daniel P. F., Wolf G. Glycoprotein biosynthesis by organ cultures of hamster trachea. Biochim Biophys Acta. 1976 Nov 18;451(1):184–200. doi: 10.1016/0304-4165(76)90270-1. [DOI] [PubMed] [Google Scholar]
  17. De Luca L. M., Sasak W., Adamo S., Bhat P. V., Akalovsky I., Silverman-Jones C. S., Maestri N. Retinoid metabolism and mode of action. Environ Health Perspect. 1980 Apr;35:147–152. doi: 10.1289/ehp.8035147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. DePierre J. W., Moron M. S., Johannesen K. A., Ernster L. A reliable, sensitive, and convenient radioactive assay for benzpyrene monooxygenase. Anal Biochem. 1975 Feb;63(2):470–484. doi: 10.1016/0003-2697(75)90371-1. [DOI] [PubMed] [Google Scholar]
  19. Dirksen E. R., Crocker T. T. Ultrastructural alterations produced by polycyclic aromatic hydrocarbons on rat tracheal epithelium in organ culture. Cancer Res. 1968 May;28(5):906–923. [PubMed] [Google Scholar]
  20. Dorman B. H., Genta V. M., Mass M. J., Kaufman D. G. Benzo(a)pyrene binding to DNA in organ cultures of human endometrium. Cancer Res. 1981 Jul;41(7):2718–2722. [PubMed] [Google Scholar]
  21. Eastman A., Mossman B. T., Bresnick E. Formation and removal of benzo(a)pyrene adducts of DNA in hamster tracheal epithelial cells. Cancer Res. 1981 Jul;41(7):2605–2610. [PubMed] [Google Scholar]
  22. Frolik C. A., Roberts A. B., Tavela T. E., Roller P. P., Newton D. L., Sporn M. B. Isolation and identification of 4-hydroxy- and 4-oxoretinoic acid. In vitro metabolites of all-trans-retinoic acid in hamster trachea and liver. Biochemistry. 1979 May 15;18(10):2092–2097. doi: 10.1021/bi00577a039. [DOI] [PubMed] [Google Scholar]
  23. Frolik C. A., Tavela T. E., Newton D. L., Sporn M. B. In vitro metabolism and biological activity of all-trans-retinoic acid and its metabolites in hamster trachea. J Biol Chem. 1978 Oct 25;253(20):7319–7324. [PubMed] [Google Scholar]
  24. GALOFRE M., PAYNE W. S., WOOLNER L. B., CLAGETT O. T., GAGE R. P. PATHOLOGIC CLASSIFICATION AND SURGICAL TREATMENT OF BRONCHOGENIC CARCINOMA. Surg Gynecol Obstet. 1964 Jul;119:51–61. [PubMed] [Google Scholar]
  25. Gallagher J. T., Kent P. W. Structure and metabolism of glycoproteins and glycosaminoglycans secreted by organ cultures of rabbit trachea. Biochem J. 1975 May;148(2):187–196. doi: 10.1042/bj1480187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Genta V. M., Kaufman D. G., Harris C. C., Smith J. M., Sporn M. B., Saffiotti U. Vitamin A deficiency enhances binding of benzo(a)pyrene to tracheal epithelial DNA. Nature. 1974 Jan 4;247(5435):48–49. doi: 10.1038/247048a0. [DOI] [PubMed] [Google Scholar]
  27. Harris C. C., Autrup H., Connor R., Barrett L. A., McDowell E. M., Trump B. F. Interindividual variation in binding of benzo[a]pyrene to DNA in cultured human bronchi. Science. 1976 Dec 3;194(4269):1067–1069. doi: 10.1126/science.982061. [DOI] [PubMed] [Google Scholar]
  28. Harris C. C., Autrup H., Stoner G. D., McDowell E. M., Trump B. F., Schafer P. Metabolism of acyclic and cyclic N-nitrosamines in cultured human bronchi. J Natl Cancer Inst. 1977 Nov;59(5):1401–1406. doi: 10.1093/jnci/59.5.1401. [DOI] [PubMed] [Google Scholar]
  29. Harris C. C., Autrup H., Stoner G. D., Trump B. F., Hillman E., Schafer P. W., Jeffrey A. M. Metabolism of benzo(a)pyrene, N-nitrosodimethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus. Cancer Res. 1979 Nov;39(11):4401–4406. [PubMed] [Google Scholar]
  30. Harris C. C., Autrup H., Stoner G., Yang S. K., Leutz J. C., Gelboin H. V., Selkirk J. K., Connor R. J., Barrett L. A., Jones R. T. Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human bronchus and pancreatic duct. Cancer Res. 1977 Sep;37(9):3349–3355. [PubMed] [Google Scholar]
  31. Harris C. C., Frank A. L., van Haaften C., Kaufman D. G., Connor R., Jackson F., Barrett L. A., McDowell E. M., Trump B. F. Binding of (3H)benzo(a)pyrene to DNA in cultured human bronchus. Cancer Res. 1976 Mar;36(3):1011–1018. [PubMed] [Google Scholar]
  32. Harris C. C., Genta V. M., Frank A. L., Kaufman D. G., Barrett L. A., McDowell E. M., Trump B. F. Carcinogenic polynuclear hydrocarbons bind to macromolecules in cultured human bronchi. Nature. 1974 Nov 1;252(5478):68–69. doi: 10.1038/252068a0. [DOI] [PubMed] [Google Scholar]
  33. Hayakawa T., Udenfriend S. A simple radioisotope assay for microsomal aryl hydroxylase. Anal Biochem. 1973 Feb;51(2):501–509. doi: 10.1016/0003-2697(73)90506-x. [DOI] [PubMed] [Google Scholar]
  34. Hill D. L., Shih T. W. Vitamin A compounds and analogs as inhibitors of mixed-function oxidases that metabolize carcinogenic polycyclic hydrocarbons and other compounds. Cancer Res. 1974 Mar;34(3):564–570. [PubMed] [Google Scholar]
  35. Ishikawa T., Takayama S., Ide F. Autoradiographic demonstration of DNA repair synthesis in rat tracheal epithelium treated with chemical carcinogen in vitro. Cancer Res. 1980 Aug;40(8 Pt 1):2898–2902. [PubMed] [Google Scholar]
  36. Jeffrey A. M., Weinstein I. B., Jennette K. W., Grzeskowiak K., Nakanishi K., Harvey R. G., Autrup H., Harris C. Structures of benzo(a)pyrene--nucleic acid adducts formed in human and bovine bronchial explants. Nature. 1977 Sep 22;269(5626):348–350. doi: 10.1038/269348a0. [DOI] [PubMed] [Google Scholar]
  37. Kahng M. W., Smith M. W., Trump B. F. Aryl hydrocarbon hydroxylase in human bronchial epithelium and blood monocyte. J Natl Cancer Inst. 1981 Feb;66(2):227–232. [PubMed] [Google Scholar]
  38. Kark J. D., Smith A. H., Switzer B. R., Hames C. G. Serum vitamin A (retinol) and cancer incidence in Evans County, Georgia. J Natl Cancer Inst. 1981 Jan;66(1):7–16. [PubMed] [Google Scholar]
  39. Kaufman D. G., Baker M. S., Harris C. C., Smith J. M., Boren H., Sporn M. B., Saffiotti U. Coordinated biochemical and morphologic examination of hamster tracheal epithelium. J Natl Cancer Inst. 1972 Sep;49(3):783–792. [PubMed] [Google Scholar]
  40. Kaufman D. G., Baker M. S., Smith J. M., Henderson W. R., Harris C. C., Sporn M. B., Saffiotti U. RNA metabolism in tracheal epithelium: alteration in hamsters deficient in vitamin A. Science. 1972 Sep 22;177(4054):1105–1108. doi: 10.1126/science.177.4054.1105. [DOI] [PubMed] [Google Scholar]
  41. Kaufman D. G. Biochemical studies of isolated hamster tracheal epithelium. Environ Health Perspect. 1976 Aug;16:99–110. doi: 10.1289/ehp.761699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Kaufman D. G., Genta V. M., Harris C. C., Smith J. M., Sporn M. B., Saffiotti U. Binding of 3H-labeled benzo(a)pyrene to DNA in hamster tracheal epithelial cells. Cancer Res. 1973 Nov;33(11):2837–2841. [PubMed] [Google Scholar]
  43. Lane B. P., Miller S. L. Carcinogen-induced changes in tracheal epithelium cultured in serum-free, chemically defined medium. J Natl Cancer Inst. 1976 May;56(5):991–996. doi: 10.1093/jnci/56.5.991. [DOI] [PubMed] [Google Scholar]
  44. Last J. A., Kaizu T., Mossman B. T. Glycoprotein synthesis by an established cell line from hamster tracheal epithelium. Exp Lung Res. 1980 Jun;1(2):89–98. doi: 10.3109/01902148009069639. [DOI] [PubMed] [Google Scholar]
  45. Last J. A., Kaizu T. Mucus glycoprotein secretion by tracheal explants: effects of pollutants. Environ Health Perspect. 1980 Apr;35:131–137. doi: 10.1289/ehp.8035131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Lechner J. F., Haugen A., Autrup H., McClendon I. A., Trump B. F., Harris C. C. Clonal growth of epithelial cells from normal adult human bronchus. Cancer Res. 1981 Jun;41(6):2294–2304. [PubMed] [Google Scholar]
  47. Lotan R., Nicolson G. L. Inhibitory effects of retinoic acid or retinyl acetate on the growth of untransformed, transformed, and tumor cells in vitro. J Natl Cancer Inst. 1977 Dec;59(6):1717–1722. doi: 10.1093/jnci/59.6.1717. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Mass M. J., Kaufman D. G. Benzo(a)pyrene quinone metabolism in tracheal organ cultures. Biochem Biophys Res Commun. 1979 Aug 13;89(3):885–892. doi: 10.1016/0006-291x(79)91861-8. [DOI] [PubMed] [Google Scholar]
  50. Mass M. J., Kaufman D. G. Species differences in the activation of benzo[a]pyrene in the tracheal epithelium of rats and hamsters. Basic Life Sci. 1983;24:331–351. doi: 10.1007/978-1-4684-4400-1_18. [DOI] [PubMed] [Google Scholar]
  51. Mass M. J., Kaufman D. G. [3H]Benzo(a)pyrene metabolism in tracheal epithelial microsomes and tracheal organ cultures. Cancer Res. 1978 Nov;38(11 Pt 1):3861–3866. [PubMed] [Google Scholar]
  52. Mettlin C., Graham S., Swanson M. Vitamin A and lung cancer. J Natl Cancer Inst. 1979 Jun;62(6):1435–1438. [PubMed] [Google Scholar]
  53. Mossman B. T., Ezerman E. B., Adler K. B., Craighead J. E. Isolation and spontaneous transformation of cloned lines of hamster tracheal epithelial cells. Cancer Res. 1980 Dec;40(12):4403–4409. [PubMed] [Google Scholar]
  54. Nebert D. W., Gelboin H. V. Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. I. Assay and properties of induced enzyme. J Biol Chem. 1968 Dec 10;243(23):6242–6249. [PubMed] [Google Scholar]
  55. 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]
  56. Nettesheim P., Snyder C., Kim J. C. Vitamin A and the susceptibility of respiratory tract tissues to carcinogenic insult. Environ Health Perspect. 1979 Apr;29:89–93. doi: 10.1289/ehp.792989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Nettesheim P., Williams M. L. The influence of vitamin A on the susceptibility of the rat lung to 3-methylcholanthrene. Int J Cancer. 1976 Mar 15;17(3):351–357. doi: 10.1002/ijc.2910170311. [DOI] [PubMed] [Google Scholar]
  58. Newton D. L., Henderson W. R., Sporn M. B. Structure-activity relationships of retinoids in hamster tracheal organ culture. Cancer Res. 1980 Oct;40(10):3413–3425. [PubMed] [Google Scholar]
  59. Pal K., Grover P. L., Sims P. The metabolism of carcinogenic polycyclic hydrocarbons by tissues of the respiratory tract. Biochem Soc Trans. 1975;3(1):174–175. doi: 10.1042/bst0030174. [DOI] [PubMed] [Google Scholar]
  60. Palekar L., Kuschner M., Laskin S. The effect of 3-methylcholanthrene on rat trachea in organ culture. Cancer Res. 1968 Oct;28(10):2098–2104. [PubMed] [Google Scholar]
  61. Palmer W. G., Allen T. J., Tomaszewski J. E. Metabolism of 7,12-dimethylbmethylbenz(a)anthracene by macrophages and uptake of macrophage-derived metabolites by respiratory tissues in vitro. Cancer Res. 1978 Apr;38(4):1079–1084. [PubMed] [Google Scholar]
  62. Roberts A. B., Frolik C. A., Nichols M. D., Sporn M. B. Retinoid-dependent induction of the in vivo and in vitro metabolism of retinoic acid in tissues of the vitamin A-deficient hamster. J Biol Chem. 1979 Jul 25;254(14):6303–6309. [PubMed] [Google Scholar]
  63. Roberts A. B., Nichols M. D., Newton D. L., Sporn M. B. In vitro metabolism of retinoic acid in hamster intestine and liver. J Biol Chem. 1979 Jul 25;254(14):6296–6302. [PubMed] [Google Scholar]
  64. Saffiotti U., Cefis F., Kolb L. H. A method for the experimental induction of bronchogenic carcinoma. Cancer Res. 1968 Jan;28(1):104–124. [PubMed] [Google Scholar]
  65. Saffiotti U., Montesano R., Sellakumar A. R., Borg S. A. Experimental cancer of the lung. Inhibition by vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors. Cancer. 1967 May;20(5):857–864. doi: 10.1002/1097-0142(1967)20:5<857::aid-cncr2820200545>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  66. Sasak W., De Luca L. M. Mannosyl transfer from mannosylretinylphosphate to glycoconjugates of rat liver membranes. FEBS Lett. 1980 Jun 2;114(2):313–318. doi: 10.1016/0014-5793(80)81141-0. [DOI] [PubMed] [Google Scholar]
  67. Schreiber H., Martin D. H., Pazmiño N. Species differences in the effect of benzo(alpha)pyrene-ferric oxide on the respiratory tract of rats and hamsters. Cancer Res. 1975 Jul;35(7):1654–1661. [PubMed] [Google Scholar]
  68. Schreiber H., Schreiber K., Martin D. H. Experimental tumor induction in a circumscribed region of the hamster trachea: correlation of histology and exfoliative cytology. J Natl Cancer Inst. 1975 Jan;54(1):187–197. doi: 10.1093/jnci/54.1.187. [DOI] [PubMed] [Google Scholar]
  69. Scott C. C., Heckman A., Nettesheim P., Snyder F. Metabolism of ether-linked glycerolipids in cultures of normal and neoplastic rat respiratory tract epithelium. Cancer Res. 1979 Jan;39(1):207–214. [PubMed] [Google Scholar]
  70. Smith D. M., Rogers A. E., Herndon B. J., Newberne P. M. Vitamin A (retinyl acetate) and benzo(alpha)pyrene-induced respiratory tract carcinogenesis in hamsters fed a commercial diet. Cancer Res. 1975 Jan;35(1):11–16. [PubMed] [Google Scholar]
  71. Smith D. M., Rogers A. E., Newberne P. M. Vitamin A and benzo(a)pyrene carcinogenesis in the respiratory tract of hamsters fed a semisynthetic diet. Cancer Res. 1975 Jun;35(6):1485–1488. [PubMed] [Google Scholar]
  72. Smith J. M., Sporn M. B., Berkowitz D. M., Kakefuda T., Callan E., Saffiotti U. Isolation of enzymatically active nuclei from epithelial cells of the trachea. Cancer Res. 1971 Feb;31(2):199–202. [PubMed] [Google Scholar]
  73. Sporn M. B., Clamon G. H., Dunlop N. M., Newton D. L., Smith J. M., Saffiotti U. Activity of vitamin A analogues in cell cultures of mouse epidermis and organ cultures of hamster trachea. Nature. 1975 Jan 3;253(5486):47–50. doi: 10.1038/253047a0. [DOI] [PubMed] [Google Scholar]
  74. Sporn M. B., Dunlop N. M., Newton D. L., Henderson W. R. Relationships between structure and activity of retinoids. Nature. 1976 Sep 9;263(5573):110–113. doi: 10.1038/263110a0. [DOI] [PubMed] [Google Scholar]
  75. Sporn M. B. Retinoids and carcinogenesis. Nutr Rev. 1977 Apr;35(4):65–69. doi: 10.1111/j.1753-4887.1977.tb06541.x. [DOI] [PubMed] [Google Scholar]
  76. Steele V. E., Marchok A. C., Nettesheim P. Oncogenic transformation in epithelial cell lines derived from tracheal explants exposed in vitro to N-methyl-N'-NITRO-N-nitrosoguanidine. Cancer Res. 1979 Oct;39(10):3805–3811. [PubMed] [Google Scholar]
  77. Stinson S. F., Reznik G., Donahoe R. Effect of three retinoids on tracheal carcinogenesis with N-methyl-N-nitrosourea in hamsters. J Natl Cancer Inst. 1981 May;66(5):947–951. [PubMed] [Google Scholar]
  78. Wardell J. R., Jr, Chakrin L. W., Payne B. J. The canine tracheal pouch. A model for use in respiratory mucus research. Am Rev Respir Dis. 1970 May;101(5):741–754. doi: 10.1164/arrd.1970.101.5.741. [DOI] [PubMed] [Google Scholar]
  79. Weinstein I. B., Jeffrey A. M., Jennette K. W., Blobstein S. H., Harvey R. G., Harris C., Autrup H., Kasai H., Nakanishi K. Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo. Science. 1976 Aug 13;193(4253):592–595. doi: 10.1126/science.959820. [DOI] [PubMed] [Google Scholar]
  80. Yang S. K., Gelboin H. V., Trump B. F., Autrup H., Harris C. C. Metabolic activation of benzo(a)pyrene and binding to DNA in cultured human bronchus. Cancer Res. 1977 Apr;37(4):1210–1215. [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES