A challenging aspect of lung carcinogenesis is the elucidation of the mechanisms which permit initiated bronchial epithelial cells to attain a growth advantage over normal bronchial epithelial cells, and subsequently evolve into a malignant phenotype. In this review, the effects of interactions between normal and transformed cells, and the potential role of representative extrinsic factors on cell-cell communication are discussed. Evidence is presented to show how cell injury and the effects of serum and calcium may affect morphology and communication, and tumor development. A large number of autocrine-paracrine factors (e.g., TGFβ, TGFα) are released by bronchial epithelial cells. These factors may inhibit or promote the proliferation of normal and transformed bronchial epithelial cells, respectively. The ability of certain injurious and tumor promoting agents (e.g., formaldehyde, TPA) to select for the transformed phenotype may involve selective cell injury, the induction of terminal differentiation and an inhibition of gap junction communication among normal BE cells.
1. Aguayo S, Kane M, King T, Schwarz M, Grauer L, and Miller Y (1988). Increased levels of a bombesin like peptide in the bronchoalveolar lavage fluid of smokers.J. Cell. Biochem.12A: 79.
2.
2. Albright CD, Frost JK, and Pressman NJ (1982). Cytologic preparations and objective morphologic analysis of cells from developing hamster squamous cell carcinomas.Analyt. Quant. Cytol.4: 141.
3.
3. Albright CD, Grimtey PM, Trump BF, Jones RT, and Resau JH (1989). Formaldehyde alters cell growth, differentiation and intercellular communication in bronchial epithelial cells in vitro.Presented at the Ninth International Washington Spring Symposium: Biology of Cellular Transducing Signals 89, Washington, D.C.
4.
4. Albright CD, Hay R, Jones RT, and Resau JH (1989). The discrimination of normal and transformed cells in vitro by cytologic and morphologic analysis.Cytotechnology2: 187–201.
5.
5. Albright CD, Jones RT, Hudson EA, Trump BF, Fontana JA, and Resau JH (1990). Transformed human bronchial epithelial cells (BEAS-2B) alter the growth and morphology of normal human bronchial epithelial cells in vitro.Cell. Biol. Toxicol. (Submitted for publication).
6.
6. Alexandersson R, Hedenstierna G, and Kalmodin-Hedman B (1989). Exposure to formaldehyde: Effects of pulmonary function.Arch. Environ. Health37: 279–284.
7.
7. Allen JG and Bloxham DP (1989). The pharmacology and pharmacokinetics of the retinoids.Pharmacol. Ther.40: 1–27.
8.
8. Arellano RO, Ramon F, Rivera A, and Zampighi GA (1988). Calmodulin acts as an intermediary for the effects of calcium on gap junctions from crayfish lateral axons.J. Membr. Biol.101: 119–131.
9.
9. Aylsworth CG, Trosko JE, and Welch CW (1986). Influence of lipids on gap junction-mediated intercellular communication between Chinese hamster cellsin vitro. Cancer Res.46: 4527–4533.
10.
10. Azamia R and Loewenstein WR (1986). Intercellular communication and the control of growth. X. Alterations of junctional permeability by the srcgene: A study with temperature-sensitive mutant Rous sarcoma virus.J. Membr. Biol.82: 191–205.
12. Baba M, Obara T, Bonfil R, Yamaguchi Y, Trump BF, Resau J, and Klein-Szanto AJP (1988). Resistance to serum-induced terminal differentiation in normal human trachcobronchial epithelial cells after in vivo exposure to 7,12-dimethylbenz-[a]anthracene.Jpn. J. Cancer Res. (Gann)79: 734–741.
13.
13. Bailey RA, Clark HM, Ferris JP, Krause S, and Strond RL (1978). Chemistry of the Environment.Academic Press, New York, p. 268.
14.
14. Bardana EJ and Andrach RH (1983). Occupational asthma secondary to low molecular weight agents used in the plastic and resin industries.Eur. J. Res-pir.Dis.64: 241–251.
15.
15. Beck LK, Kane MA, and Bunn PA (1988). Innovative and future approaches to small cell lung cancer treatment.Seminars Oncol.15: 300–314.
16.
16. Beeman DK, Siegfried JM, and Mass MJ (1987). Effect of phorbol esters on clonal cultures of human, hamster, and rat respiratory epithelial cells.Cancer Res.47: 541–546.
17.
17. Beer DG, Neyeu MJ, Paul DL, Rapp UR, and Pitot HC (1988). Expression of the c-raf protooncogene, gamma-glutamyltranspeptidasc, and gap junction protein in rat liver neoplasm.Cancer Res.48: 1610–1617.
18.
18. Bergh J (1988). The expression of the platelet-derived and transforming growth factor genes in human non-small lung cancer cell lines is related to tumor stroma formation in nude mice tumors.Am. J. Pathol133: 434–439.
19.
19. Borck C, Higashino S, and Loewenstein WR(1969). Intercellular communication and tissue growth. IV. Conductance of membrane junctions or normal and cancerous cells in culture.J. Membr. Biol.1: 274–293.
20.
20. Boyd FT and Massagué J (1989). Transforming growth factor-β inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor.J. Biol. Chem.264: 2272–2278.
21.
21. Budunova IV, Mittleman LA, and Belitsky GA (1989). Identification of tumor promoters by their inhibitory effect on intercellular transfer of lucifer yellow.Cell Biol. Toxicol.5: 77–89.
22.
22. Caspar DLD, Goodenough DA, Makowski L, and Phillips WC (1977). Gap junction structures. I. Correlated electron microscopy and x-ray diffraction.J. Cell. Biol.74: 605–628.
23.
23. Carney DN, Cuttita F, Moody TW, and Minna JD (1987). Selective stimulation of small cell lung cancer clonal growth by bombesin and gastrin-releasing peptide.Cancer Res.47: 821–825.
24.
24. Caveny S (1985). The role of gap junctions in development.Ann. Rev. Physiol.47: 319–335.
25.
25. Chang C-C, Trosko JE, Jung H-J, Bombick D, and Matsumura F (1985). Potential role of the src gene product in inhibition of gap-junctional communication in NIH/3T3 cells.Proc. Natl. Acad. Sci. USA.82: 5360–5364.
26.
26. Cromack DT, Sporn MB, Roberts AB, Merino MJ, Dart LL, and Norton JA (1987). Transforming growth factor beta levels in rat wound chambers.J. Surg. Res.42: 622–628.
27.
27. Cuttita F, Carney DN, Mulshine J, Moody TW, Fedorko J, Fischler A, and Minna JD (1985). Bom-besin-like peptides can function as autocrine growth factors in human small cell lung cancer.Nature316: 823–826.
28.
28. Dalbey WE (1982). Formaldehyde and tumors in hamster respiratory tract.Toxicology24: 9–14.
29.
29. Darnell JE, Lodish HF, and Baltimore D (1986). Molecular Biology.W. H. Freeman and Co., New York, pp. 667–713.
30.
30. Davidson JS, Baumgarten IM, and Harley EH (1985). Studies on the mechanism of phorbol ester-induced inhibition of intercellular junctional communication.Carcinogenesis6: 1353–1358.
31.
31. DeMello WC (1984). Modulation of junctional permeability.Fed. Proc.43: 2692–2696.
32.
32. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS, and Berger WH (1987). Synthesis of mRNAs for transforming growth factors α and β and the epidermal growth factor receptor by human tumor cells.Cancer Res.47: 707–712.
33.
33. Duniec ZM, Eling TE, Jetton AM, Gray TE, and Nettesheim P (1989). Arachidonic acid metabolism in normal and transformed rat tracheal epithelial cells and its possible role in the regulation of cell proliferation.Exp. Lung Res.15: 391–408.
34.
34. Dvorak HF (1986). Tumors Wounds that do not heal.N. Engl. J. Med.315: 1650–1659.
35.
35. Emura M, Mohr U, Riebe M, Aufderheide M, and Dungworth DL (1988). Regulation of growth and differentiation by vitamin A in a cloned fetal lung epithelial cell line cultured on collagen gel in hormone-supplemented medium.In Vitro Cell Dev. Biol.24: 639–648.
36.
36. Enomoto T and Yamasaki H (1984). Lack of intercellular communication between chemically transformed and surrounding nontransformed BALB/c 3T3 cells.Cancer Res.44: 5200–5203.
37.
37. Fallon RF and Goodenough DA (1981). Five hour half-life of mouse liver gap junction protein.J. Cell. Biol.90: 521–526.
38.
38. Favennec L and Cals M-J (1988). The biologic effects of retinoids on cell differentiation and proliferation.J. Clin. Chem. Clin. Biochem.26: 479–489.
39.
39. Florey H, Carleton HM, and Wells AQ (1932). Mucus secretion in the trachea.Br. J. Exp. Pathol.13: 269–284.
40.
40. Forastiere F, Lagorio S, Michelozzi P, Canariani F, Arca’ M, Borgia P, Perucci C, and Axelson O, (1986). Silica, silicosis and lung cancer among ceramic workers: A case-referent study.Am. J. Ind. Med.10: 363–370.
41.
41. Frost JK, Gupta PK, Erozan YS, Carter D, Hollander DH, Levin ML, and Ball WC (1973). Pulmonary cytologic alterations in toxic environmental inhalation.Hum. Pathol.4: 521–536.
42.
42. Frost JK, Erozan YS, Gupta PK, and Carter D (1983). Cytopathology. In: Atlas of Early Lung Cancer.Igaku-Shoin, Inc., New York, pp. 33–76.
43.
43. Frost JK, Pressman NJ, Gill GW, Showers RL, Bitman WR, Frost Jr JK, and Albright CD (1983). Quantitative nuclear analysis of developing squa-mous cell carcinoma of the human lung.Analyt. Quant. Cytol.5: 207.
44.
44. Fullmer CD, Short JG, Allen A, and Walker K (1969). Proposed classification for bronchial epithelial cell abnormalities in the category of dyskaryosis.Acta Cytol.13: 459–471.
45.
45. Furstenberger G, Rogers M, Schnapke R, Bauer G, Hoffer P, and Marks F (1989). Stimulatory role of transforming growth factors in multistage skin carcinogenesis: Possible explanation for the tumor-inducing effect of wounding in initiated NMRI mouse skin.Int. J. Cancer43: 915–921.
46.
46. Genta VM, Kaufman DG, Harris CC, Smith JM, Sporn MB, and Saffiotti U (1974). Vitamin A deficiency enhances binding of benzo[a]pyrene to tracheal epithelial DNA.Nature247: 48–49.
47.
47. Gilula NB (1984). The biosynthesis of gap junctions.Fed. Proc.32: 2678–2680.
48.
48. Goldman WE and Baseman JB (1980). Glycopro-tein secretion by cultured hamster tracheal epithelial cells: A model for in vitro studies of mucus synthesis.In Vitro Cell Dev. Biol.16: 320–329.
49.
49. Gonzalez FA, Rozengurt E, and Heppel LA (1989). Extracellular ATP induces the release of calcium from intracellular stores without the activation of protein kinase C in Swiss 3T6 mouse fibroblasts.Proc. Natl. Acad. Sci. USA86: 4530–4534.
50.
50. Goodenough DA (1979). Gap junction dynamics and intercellular communication.Pharmacol. Rev.30: 383–392.
51.
51. Gordon RE, Lane BR, and Marin M (1982). Regeneration of rat tracheal epithelium: Changes in gap junctions during specific phases of the cell cycle.Exp. Lung Res.3: 47–56.
52.
52. Gorman RR, Wieranga W, and Miller OV (1979). Independence of the cyclic AMP-lowering activity of thromboxane A2 from the platelet release reaction.Biochem. Biophys. Acta572: 95–104.
53.
53. Grafstrom RC, Curren RD, Yang LL, and Harris CC (1985). Genotoxicity of formaldehyde in cultured human bronchial fibroblasts.Science228: 89–90.
54.
54. Grandjean P, Andersen O, and Nielsen GD (1988). Carcinogenicity of occupational nickel exposures: An evaluation of the epidemiological evidence.Am. J. Ind. Med.13: 193–209.
55.
55. Greenblatt M (1988). Formaldehyde toxicity: A review of recent research and regulatory changes.Lab. Med.19: 425–428.
56.
56. Hahon N and Castranova V (1989). Interferon production in rat type II pneumocytes and alveolar macrophages.Exp. Lung Res.15: 429–445.
57.
57. Hamada J-I, Takeichi N, and Kobayashi H (1988). Metastatic capacity and intercellular communication between normal cells and metastatic cell clones derived from rat mammary carcinoma.Cancer Res.48: 5129–5132.
58.
58. Hamaguchi M and Hanafusa H (1989). Localization of major potential substrates of p60 kinase in the plasma membrane.Oncogene Res.4: 29–37.
59.
59. Harris CC, Willey JC, Saladino AJ, and Grafstrom RC (1985). Effects of tumor promoters, aldehydes, peroxides, and tobacco smoke condensate on growth and differentiation of cultures normal and transformed human bronchial cells. In: Cocarcinogene-sis—A Comprehensive Survey. Vol 8, Cancer of the Respiratory Tract—Predisposing Factors, MJ Mass (ed). Raven Press, New York, pp. 159–171.
60.
60. Harris H and Bramwell ME (1987). The suppression of malignancy by terminal differentiation: Evidence from hybrids between tumor cells and keratinocytes.J. Cell Sci.87: 383–388.
61.
61. Hebert CD and Birnbaum LS (1989). Lack of correlation between sensitivity to growth inhibition and receptor number for transforming factor β in human squamous carcinoma cell lines.Cancer Res.49: 3196–3202.
62.
62. Hennings H, Kruszewski FH, Yuspa SH, and Tucker R (1989). Intercellular calcium alterations in response to increased external calcium in normal and neoplastic keratinocytes.Carcinogenesis10: 777–780.
63.
63. Hesterberg TW, Maness SC, Iglehart JD, Sanchez JH, and Boreiko CJ (1987). Subpopulations of human bronchial epithelial cells in culture respond heterogeneously to 12–0-tetradecanoylphorbol-13-acetate (TPA) and other modulators of differentiation.Carcinogenesis8: 1511–1515.
64.
64. Hosoi K and Edidin M (1989). Exogenous ATP and other nucleoside phosphates modulate epidermoid growth factor receptors of A-431 epidermoid carcinoma cells.Proc. Natl. Acad. Sci. USA86: 4510–4514.
65.
65. Huang FL, Roop DR, and De Luca LM (1986). Vitamin A deficiency and keratin biosynthesis in cultured hamster trachea.In Vitro Cell Dev. Biol.22: 223–230.
66.
66. Hunter T and Cooper J (1985). Protcin-tyrosine ki-nases.Am. Rev. Biochem.54: 897–930.
67.
67. Hwang DL, Tay Y-C, Lin SS, and Lev-Ran A (1986). Expression of epidermal growth factor receptors in human lung tumors.Cancer58: 2260–2263.
68.
68. Imanishi K, Yamaguchi K, Suzuki M, Honda S, Yanaihara N, and Abe K (1989). Production of transforming growth factor—α in human tumour cell lines.Br. J. Cancer59: 761–765.
69.
69. Inoue S and Hogg JC (1977). Freeze-etch study of the tracheal epithelium of normal guinea pigs with particular reference to intercellular junctions.J. Ul-trastruc. Res.61: 89–99.
70.
70. Inoue S and Richardson JB (1979). A correlated thin section and freeze-fracture study of mouse tracheal epithelium before and after ether anesthesia.Lab. Invest.40: 583–585.
71.
71. Janik P, Assof A, and Bertram JS (1980). Inhibition of growth to primary and metastatic Lewis lung carcinoma cells by the phosphodiesterase inhibitor iso-butylmethylxanthine.Cancer Res.40: 1950–1954.
72.
72. Jetten AM and Shirley JE (1983). Retinoids antagonize the induction of ornithine decarboxylase activity by phorbol esters and phospholipase C in rat tracheal epithelial cells.J. Cell. Physiol.123: S14–S20.
73.
73. Jetten AM, George MA, Pettit GR, and Rearick JI (1989). Effects of bryostatins and retinoic acid on phorbol ester- and diacylglycerol-induced squamous differentiation in human tracheobronchial epithelial cells.Cancer Res.49: 3990–3995.
74.
74. Jetten AM, George MA, Smits HL, and Vollberg TM (1989). Keratin 13 expression is linked to squamous differentiation in rabbit tracheal epithelial cells and down-regulated by retinoic acid.Exp. Cell Res.182: 622–634.
75.
75. Johnston WW and Bossen EH (1981). Ten years of respiratory cytopathology at Duke University Medical Center. II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer.Acta Cytol.25: 499–505.
76.
76. Jones RT and Elliget KA (1987). Method for the culture of human bronchial epithelial cells from tissues obtained at extended post-mortem intervals.In Vitro Cell Dev. Biol.23: 36A.
77.
77. Jullien P, Berg TM, and Lawrence DA (1989). Acidic cellular environments: Activation of latent TGF-β and sensitization of cellular responses to TGF-β and EGF.Int. J. Cancer43: 886–891.
78.
78. Keenan KP, Combs JW, and McDowell EM (1982). Regeneration of hamster tracheal epithelium after mechanical injury. I. Focal lesions: Quantitative morphologic study of cell proliferation.Virch. Arch. B. [Cell Pathol.]41: 193–214.
79.
79. Keenan KP, Saffiotti U, Stinson SF, Riggs CW, and McDowell EM (1989). Morphological and cytoki-netic responses of hamster airways to intralaryngcal or intratracheal cannulation with instillation of saline or ferric oxide particles in saline.Cancer Res.49: 1521–1527.
80.
80. King RJ, Jones MB, and Minoo P (1989). Regulation of lung cell proliferation by polypeptide growth factors.Am. J. Physiol.257: L23–L38.
81.
81. Klein JH and Adamson IYR (1989). Fibroblast inhibition and prostaglandin secretion by alveolar epithelial cells exposed to silica.Lab. Invest.60: 808–813.
82.
82. Klein-Szanto AJP (1987). Models for the study of experimental tracheobronchial neoplasias. In: Lung Carcinomas, EM McDowell (ed). Churchill Livingstone, London, pp. 175–205.
83.
83. Klein-Szanto AJP, Baba M, Trono D, Obara T, Resau J, and Trump BF (1986). Epidermoid metaplasias of xenotransplanted human tracheobronchial epithelium.Carcinogenesis7: 987–994.
84.
84. Klein-Szanto AJP, Topping DC, Heckman CA, and Nettesheim P (1980). Ultrastructural characteristics of carcinogen-induced dysplastic changes in tracheal epithelium.Am. J. Pathol.98: 83–100.
85.
85. Kotin P (1968). Carcinogenesis of the lung: Environmental and host actors. In: The Lung, AA Liebow and DE Smith (eds). Williams and Wilkins, Baltimore, pp. 203–225.
86.
86. Kulesz-Martin MF, Koehler B, Hennings H, and Yuspa SH (1980). Quantitative assay for carcinogen altered differentiation in mouse epidermal cells.Carcinogenesis1: 995–1006.
87.
87. Lane BP and Gordon R (1974). Regeneration of rat tracheal epithelium after mechanical injury. I. The relationship between mitotic activity and cellular differentiation.Proc. Soc. Exp. Biol. Med.145: 1139–1144.
88.
88. Lechner JF and La Veck MA (1985). A serum-free method for cultivating normal human bronchial and epithelial cells at clonal density.J. Tissue Culture Methods9: 43–48.
89.
89. Lechner JF, Haugen A, Autrup H, McClendon IA, Trump BF, and Harris CC (1981). Clonal growth of epithelial cells from normal adult human bronchus.Cancer Res.41: 2294–2304.
90.
90. Lechner JF, McClendon IA, La Veck MA, Shamsuddin AM, and Harris CC (1983). Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells.Cancer Res.43: 5915–5921.
91.
91. Lechner JF, Haugen A, McClendon IA, and Shamsuddin AM (1984). Induction of squamous differentiation of normal human bronchial epithelial cells by small amount of serum.Differentiation25: 229–237.
92.
92. Leslie CC, McCormick-Shannon K, and Mason RJ (1989). Bronchoalvcolar lavage fluid from normal rats stimulates DNA synthesis in rat alveolar type II cells.Am. J. Rcsp. Dis.139: 360–366.
93.
93. Loeb LA, Emster VL, Warner KE, Abbotts J, and Laszlo J (1984). Smoking and lung cancer: An overview.Cancer Res.44: 5940–5958.
94.
94. Loewenstein WR (1979). Junctional intercellular communication and the control of growth.Biochim. Biophys. Acta560: 1–65.
96. Loewenstein WR (1987). The cell-to-cell channel of gap junctions.Cell48: 725–726.
97.
97. Macaulay V, Teale JD, and Everard M (1987). So-matomedin-C/insulin-like growth factor I is a mi-togen for human small cell lung cancer (SCLC).Proc. Am. Assoc. Cancer Res.28: 213.
98.
98. Madhukar BV, Oh SV, Chang CC, Wade M, and Trosko JE (1987). Altered regulation of intercellular communication by epidermal growth factor, transforming growth factor-β and peptide hormones in normal human keratinocytes.Carcinogenesis10: 13–20.
99.
99. Maldonado PE, Rose B, and Loewenstein WR (1988). Growth factors modulate junctional cell-to-ccll communication.J. Membr. Biol.106: 203–210.
100.
100. Marchok AC, Rhoton JC, Griesemer RA, and Nettesheim P (1977). Increased in vitro growth capacity of tracheal epithelium exposed in vivo to 7,12-di-methylbenz[a]anthracene.Cancer Res.37: 1811–1821.
101.
101. Masui T, Wakcfield LM, Lechner JF, La Veck MA, Sporn MB, and Harris CC (1986). Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells.Proc. Natl. Acad. Sci. USA83: 2438–2442.
102.
102. McCollum EV and Davis M (1913). The necessity of certain lipids in the diet during growth.J. Biol. Chem.15: 167–175.
103.
103. McDowell EM, Barrett LA, Glavin F, Harris CC, and Trump BF (1978). The respiratory epithelium. I. Human bronchus.J. Natl. Cancer Inst.61: 539–549.
104.
104. McDowell EM, Ben T, Coleman B, Chang S, New-kirk C, and De Luca LM (1987). Effects of retinoic acid on the growth and morphology of hamster tracheal epithelial cells in primary culture.Virch. Arch. B. [Cell.Pathol.]54: 38–51.
105.
105. McDowell EM and Trump BF (1983). Histogenesis of preneoplastic and neoplastic lesions in tracheobronchial epithelium.Surv. Synth. Path. Res.2: 235–279.
106.
106. Mehta PP, Bertram JS, and Loewenstein WR (1986). Growth inhibition of transformed cells correlates with their junctional communication with normal cells.Cell44: 187–196.
107.
107. Menon GK, Grayson S, and Elias PM (1985). Ionic calcium reservoirs in mammalian epidermis: Ultra-structural localization by ion-capture cytochemistry.J. Invest. Dermatol.84: 508–512.
108.
108. Mesnil M and Yamasaki H (1988). Selective gapjunctional communication capacity of transformed and non-transformed rat liver epithelial cell lines.Carcinogenesis9: 1499–1502.
109.
109. Meyer DD, Yancey SB, and Revel JP (1981). Intercellular communication in normal and regenerating rat liver A quantitative analysis.J. Cell. Biol.91: 505–523.
110.
110. Miller BE, Miller FR, Wilburn D, and Hepncr GH (1988). Dominance of a tumor subpopulation in mixed heterogeneous mouse mammary tumors.Cancer Res.48: 5747–5753.
111.
111. Miyashita M, Smith MW, Willey JC, Lechner JF, Trump BF, and Harris CC (1989). Effects of serum, transforming growth factor beta, or 12-O-tetrade-canoylphorbol-13-acetate on ionized calcium concentration in normal and transformed human bronchial epithelial cells.Cancer Res.49: 63–67.
112.
112. Monteiro-Riviere NA, and Popp JA (1986). Ultra-structural evaluation of acute nasal toxicity in the rat respiratory epithelium in response to formaldehyde gas.Fund. Appl. Toxicol.6: 251–262.
113.
113. Monticello TM, Morgan KT, Everitt JI, and Popp JA (1989). Effects of formaldehyde gas on the respiratory tract of Rhesus monkeys.Am. J. Pathol.134: 515–527.
114.
114. Mori M, Naito R, Tsukitani K, Okada Y, and Tsujimura T (1989). Widespread distribution of human epidermal growth factor (hEGF) in human tissues and organs under normal and tumorous conditions— Immunohistochcmical studies with the use of polyclonal and monoclonal antibodies.Acta Histochem. Cytochem.22: 15–34.
115.
115. Mossman BT, Kessler JB, Ley B\V, and Craighead JE (1977). Interaction of crocidolite asbestos with hamster respiratory mucosa in organ culture.Lab. Invest.36: 131–139.
116.
116. Mossman BT, Cameron GS, and Yotti LP (1985). Cocarcinogenic and tumor promoting properties of asbestos and other minerals in tracheobronchial epithelium. In: Cocarcinogenesis—A Comprehensive Suney, Vol 8, Cancer of the Respiratory Tract— Predisposing Factors, MJ Mass (ed). Raven Press, New York. pp. 159–171.
117.
117. Mur JM, Meyer-Bisch C, Pham QT, Massin N, Moulin JJ, Cavalier C, and Sadoul P (1987). Risk of lung cancer among iron ore miners: A proportional mortality study of 1,075 deceased miners in Lorraine, France.J. Occup. Med.29: 762–768.
118.
118. Nasiell M (1966). Metaplasia and atypical metaplasia in the bronchial epithelium. A histopathologic and cytopathologic study.Acta Cytol.10: 421–427.
119.
119. Nasiell M, Kato H, Auer G, Zetterberg A, Roger V, and Karlen L (1978). Cytomorphological grading and Feulgen DNA analysis of metaplastic and neo-plastic bronchial cells.Cancer41: 1511–1521.
120.
120. Nelson N, Levine RJ, Albert RE, Blair AE, Griesemer RA, Landrigan PJ, Stayncr LT, and Swenberg JA (1986). Contribution of formaldehyde to respiratory cancer.Environ. Health Perspec.77: 23–35.
121.
121. Nettesheim P and Griesemer RA (1978). Experimental models for studies of respiratory tract carcinogenesis. In: Pathogenesis and Therapy of Lung Cancer, Vol 10, Lung Biology in Health and Disease, CC Harris (ed). M Dekker, Inc., New York, pp. 75–188.
122.
122. Nettesheim P and Schreiber H (1975). Advances in experimental lung cancer research. In: Handbuch der allgemeinen Pathologie, Sixth volume: Tumors, part 7, E Grundman (ed). Springer-Verlag, Berlin, pp. 603–691.
123.
123. Nettesheim P, Smits HL, George MA, Gray T, and Jetten AM (1989). Squamous differentiation in normal and transformed rat tracheal epithelial cells.Carcinogenesis10: 743–748.
124.
124. Nettesheim P and Yarita T (1979). Studies with a new experimental model in respiratory carcinogenesis.Prog. Exp. Tumor Res.24: 330–344.
125.
125. Nettesheim P, Schreiber H, Creasia DA, and Richter CB (1974). Respiratory infections and the pathogenesis of lung carcinomas.Recent Results Cancer Res.44: 138–157.
126.
126. Newsome JR, Norman V, and Keith CH (1965). Vapor phase analysis of tobacco smoke.Tobacco Sci.9: 102–110.
127.
127. Newton DL, Henderson \VL, and Spom MB (1980). Structure-activity relationships of retinoids in hamster tracheal organ culture.Cancer Res.40: 3413–3425.
128.
128. Nishizuka Y (1986). Studies and perspectives of protein kinase C.Science233: 305–312.
129.
129. Nylen ES, Linnoila RI, and Becker KL (1988). Prenatal cholinergic stimulation of pulmonary neuroendocrinc cells by nicotine.Acta Physiol. Scand.132: 117–118.
130.
130. Paul DL (1986). Molecular cloning of cDNA for rat liver gap junction protein.J. Cell. Biol.103: 123–134.
131.
131. Pircher R, Jullien P, and Lawrence DA (1986). β-Transforming growth factor is stored in human blood platelets as a latent high molecular weight complex.Biochem. Biophys. Res. Comm.136: 30–37.
132.
132. Peracchia C and Bernardini G (1984). Gap junction structure and cell-cell coupling regulation: Is there a calmodulin involvement?Fed. Proc.43: 2681–2691.
133.
133. Peracchia C, Bernardini G, and Peracchia LL (1983). Is calmodulin involved in the regulation of gap junction permeability?Pfleugers Arch.399: 152–154.
134.
134. Pressman NJ, Frost JK, and Albright CD (1983). Quantitative nuclear analysis of developing squamous cell carcinoma of the hamster check pouch.Analyt. Quant. Cytol.5: 216.
135.
135. Radu A, Dahl G, and Loewenstein WR (1982). Hormonal regulation of cell junction permeability: Up regulation by catecholamine and prostaglandin E.J. Membr. Biol.70: 239–251.
136.
136. Reddel RR, Ke Y, Gerwin BI, McMenamin MG, Lechner JF, Su RT, Brash DE, Park J-B, Rhim JS, and Harris CC (1988). Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprccipitation with a plas-mid containing SV40 early region genes.Cancer Res.48: 1904–1909.
137.
137. Reddel RR, Ke Y, Kaighn ME, Malan-Shibley L, Lechner JF, Rhim JS, and Harris CC (1988). Human bronchial epithelial cells neoplastically transformed by v-Ki-ras: Altered response to inducers of terminal squamous differentiation.Oncogene Res.3: 401–408.
138.
138. Revel JP and Karanovsky MJ (1967). Hexagonal array of subunits in intercellular junctions of the mouse heart and lens.J. Cell. Biol.33: C7.
139.
139. Revel JP, Nicholson BJ, and Yancey SB (1984). Molecular organization of gap junctions.Fed. Proc.43: 2672–2677.
140.
140. Rivera RT, Pasion SG, Wong DTW, Fei Y, and Biswas DK (1989). Loss of tumorigenic potential by human lung tumor cells in the presence of antisense RNA specific to the ectopically synthesized alpha subunit of human chorionic gonadotropin.J. Cell. Biol.108: 2423–2434.
141.
141. Rutten AAJJL, Wilmer JWGM, and Beems RB (1988). Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. I. A cell proliferation study.Virch. Arch. B. [Cell Pathol.]55: 167–175.
142.
142. Rutten AAJJL, Beems RB, and Wilmer JWGM (1988). Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. II. A histomorphological study.Virch. Arch. B [Cell Pathol.]55: 177–186.
143.
143. Rutten AAJJL, Jongen WMF, de Haan LHJ, Hen-driksen EGJ, and Koeman JH (1988). Effect of reti-nol and cigarette smoke condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells.Carcinogenesis9: 315–320.
144.
144. Saccomanno G, Saunders RP, Archer VE, Auerbach O, Kuschner M, and Beckler PA (1965). Cancer of the lung: The cytology of sputum prior to the development of carcinoma.Acta Cytol.9: 413–423.
145.
145. Saccomanno G, Archer VE, Auerbach O, Saunders RP, and Brennan LM (1974). Development of carcinoma of the lung as reflected in exfoliated cells.Cancer32: 256–270.
146.
146. Sacz JC, Connor JA, Spray DC, and Bennett MVL (1989). Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions.Proc. Natl. Acad. Sci. USA86: 2708–2712.
147.
147. Saez JC, Gregory WA, Watanabe T, Dermeitzel R, Hertzberg EL, Reid L, Bennett MVL, and Spray DC (1989). cAMP delays disappearance of gap junctions between pairs of rat hepatocytes in primary culture.Am. J. Physiol.257: C1–C11.
149. Saffiotti U (1970). Experimental respiratory tract carcinogcncsis and its relation to inhalation exposures. In: Inhalation Carcinogenesis. MG Hanna, P Nettesheim, and JR Gilbert (eds). Atomic Energy Commission Symposium ser. 18, National Technical Information Service, Springfield, pp. 27–54.
150.
150. Saffiotti U, Montesano R, Sellakumar AR, and Borg SA (1967). Experimental cancer of the lung. Inhibition by vitamin A of tracheal-bronchial squamous metaplasia and squamous cell tumors.Cancer20: 857–864.
151.
151. Saffiotti U, Cefis F, and Kolb LH (1968). A method for the experimental induction of bronchogenic carcinoma.Cancer Res.28: 104–124.
152.
152. Saito Y, Imai T, Sato M, Ota S-I, Kanna K, Takaha-shi S, Usuda K, Sagawa M, Maganoto N, Suda H, and Nakada T (1988). Cytologic study of tissue repair in human bronchial epithelium.Acta Cytol.32: 622–628.
153.
153. Saladino AJ, Willey JC, Lechner JF, Grafstrom RC, LaVeck M, and Harris CC (1985). Effects of formaldehyde, acetaldehyde, benzoyl peroxide, and hydrogen peroxide on cultured normal human bronchial epithelial cells.Cancer Res.45: 2522–2526.
154.
154. Sastrodihardjo S, Sasaki Y, Shiba Y, and Kanno Y (1987). Possible involvement of reorganization of actin filaments, induced by tumor-promoting phorbol esters, in changes in colony shape and enhancement of proliferation of cultured epithelial cells.J. Cell. Physiol.132: 49–56.
155.
155. Schiff LJ and Moore SJ (1985). Effects of cyclic adenosine 3':5'-monophosphate-elevating agents and re-tinoic acid on differentiation in retinoid-deficient tracheal cultures.In Vitro Cell Dev. Biol.21: 688–692.
156.
156. Schneebergcr EE (1980). Heterogeneity of tight junction morphology in extrapulmonary and intrapulmonary airways of the rat.Anat.Rec.198: 193–208.
157.
157. Schneeberger EE, Walters DV, and Oliver RE (1978). Development of intercellular junctions in the pulmonary epithelium of the fetal lamb.J. Cell Sci.32: 307–324.
158.
158. Schreiber H, Bibbo M, Wied GL, Saccomanno F, and Nettesheim P (1979). Bronchial metaplasia as a benign or premalignant lesion. I. Cytologic and ultrastructural discrimination between acute carcinogen effects and toxin-induced changes.Acta Cytol.23: 496–503.
159.
159. Schultz GS, White M, Mitchell R, Brown G, Lynch J, Twardzik DR, and Todaro GJ (1987). Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor.Science235: 350–352.
160.
160. Selikoff IJ, Hammond EC, and Churg J (1968). Asbestos exposure, smoking and neoplasia.J. Am. Med. Assoc.204: 106–111.
161.
161. Sesko AM and Mossman BT (1989). Sensitivity of hamster tracheal epithelial cells to asbestiform minerals modulated by serum and by transforming growth factor β.Cancer Res.49: 2743–2749.
162.
162. Shen V, Rifas L, Kohler G, and Peck WA (1986). Prostaglandins change cell shape and increase intercellular gap junctions in osteoblastscultured from rat fetal calvaria.J. Bone Miner. Res.1: 243–249.
163.
163. Sherwin SA, Minna JD, Gazdar AF, and Todaro GJE (1981). Expression of epidermal and nerve growth factor receptor and soft agar growth factor production by human lung cancer cells.Cancer Res.41: 3538–3542.
164.
164. Shiba M, Marchok AC, and Klein-Szanto AJP (1983). An open-ended rat tracheal implant model: Toxic effects of formaldehyde on the respiratory epithelium.Toxicol. Letters16: 241–248.
165.
165. Shiba M, Marchok AC, Klein-Szanto AJP, and Ya-maguchi Y (1987). Pathological changes induced by formaldehyde in open-ended rat tracheal implants pre-exposed to benzo[a]pyrcne.Toxicol. Pathol.15: 401–408.
166.
166. Smith MW, Ambudkar IS, Phelps PC, Regec AL, and Trump BF (1987). HgCI2-induced changes in cytosolic Ca2+ of cultured rabbit renal tubular cells.Biochem. Biophys. Acta931: 130–142.
167.
167. Smith MW, Jones RT, Willey JC, Harris C, and Trump BF (1988). The effect of H2O2 and formaldehyde on [Ca2+], or normal and transformed human bronchial epithelial cells.FASEB. J.2: A407.
168.
168. Snyder CE, Nadziejko CE, and Herp A (1984). Human bronchial explants in long-term culture: Establishing a baseline for secretion.In Vitro Cell Dev. Biol.20: 95–102.
169.
169. Sporn MB and Roberts AB (1986). Peptide growth factors and inflammation, tissue repair and cancer.J. Clin. Invest.78: 329–332.
170.
170. Sporn MB, Dunlop NM, Newton DL, and Smith JM (1976). Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids).Fed. Proc.35: 1332–1338.
171.
171. Sporn MB, Roberts AB, Roche NS, Kagechika H, and Shudo K (1986). Mechanism of action of retinoids.J. Am. Acad. Derm.15: 756–764.
172.
172. Sporn MB, Roberts AB, Wakefield LM, and Assoian RK (1986). Transforming growth factor-beta: Biological function and chemical structure.Science233: 532–534.
173.
173. Sporn MB and Todaro GJ (1980). Autocrine secretion and malignant transformation of cells.N. Engl. J. Med.303: 878–880.
174.
174. Stahlman MT, Orth DN, and Gray ME (1989). Im-munocytochemical localization of epidermal growth factor in the developing human respiratory system and in acute and chronic lung disease in the neonate.Lab. Invest.60: 539–547.
175.
175. Sutherland RM (1986). Importance of critical metabolites and cellular interactions in the biology of microregions of tumors.Cancer38: 1668–1680.
176.
176. Swenberg JA, Barrow CS, Boreiko CJ, Heck H d'A, Levine RJ, Morgan KT, and Starr TB (1983). Nonlinear responses to formaldehyde and their implications for carcinogenic risk assessment.Carcinogenesis4: 945–952.
177.
177. Tabassian AR, Nylen ES, Linnoila RI, Snider RH, Cassidy MM, and Becker KL (1989). Stimulation of hamster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke.Am. Rev. Resp. Dis.140: 436–440.
178.
178. Tachikawa T, Yamamura T, and Yoshiki S (1984). Changes occurring in plasma membranes and intercellular junctions during the process of carcino-genesis and in squamous cell carcinoma.Virch. Arch. B. [Cell Pathol.]47: 1–15.
179.
179. Tachikawa T, Kohno Y, Matsui Y, and Yoshiki S (1986). In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.Car-cinogenesis7: 885–892.
180.
180. Takeda A, Hashimoto E, Yamamura H, and Shi-mazu T (1987). Phosphorylation of liver gap junction protein by protein kinase C.FEBS. Letters210: 169–172.
181.
181. Terzaghi-Howe M (1987). Inhibition of carcinogen-altered rat tracheal epithelial cell proliferation by normal epithelial cellsin vivo. Carcinogenesis8: 145–150.
182.
182. Thomassen DG, Gray TE, Mass MJ, and Barrett JC (1983). High frequency of carcinogen-induced early preneoplastic changes in rat tracheal epithelial cells in culture.Cancer Res.43: 5956–5963.
183.
183. Topping DC and Nettesheim P (1980). Two-stage carcinogencsis studies with asbestos in Fischer 344 rats.J. Natl. Cancer Iust.65: 627–630.
184.
184. Trosko JE and Chang CC (1988). Chemical and on-cogene modulation of gap junctional intercellular communication. In: Tumor Promoters: Biological Approaches for Mechanistic Studies and Assay Systems, R Langenbach, E Elmorc, and JC Barrett (eds). Raven Press, New York, pp. 97–111.
185.
185. Trosko JE, Yotti LP, Warren ST, Tsuchimoto G, and Chang CC (1982). Inhibition of cell-cell communication by tumor promoters. In: Carcinogenesis, E Hecker, NE Fusenig, W Kunz, F Marks, and HE Thielman (eds). Raven Press, New York, Vol 7, pp. 568–585.
186.
186. Trosko JE, Jone C, and Chang CC (1984). Oncogenes, inhibited intercellular communication and tumor promotion. In: Cellular Interactions by Environmental Tumor Promoters, H Fujiki (ed). Japan Sci Soc Press, Tokyo/VNU Science Press, Utrecht, pp. 101–113.
187.
187. Trump BF and Berezesky IK(1987). Ion regulation, cell injury and carcinogencsis.Carcinogenesis8: 1027–1032.
188.
188. Trump BF, McDowell EM, Glavin F, Barrett LA, Becci PJ, Schurch W, Kaiser HE, and Harris CC (1978). The respiratory epithelium. III. Histogenesis of epidermoid metaplasia and carcinoma in situ in the human.J. Natl. Cancer Inst.61: 563–575.
189.
189. Trump BF, Resau J, and Barrett LA (1980). Methods of organ culture for human bronchus. In: Methods in Cell Biology, CC Harris, BF Trump, and GD Stoner (eds). Academic Press, New York, pp. 1–14.
190.
190. Trump BF, Berezesky IK, Smith MW, Phelps PC, and Elliget KA (1989). The relationship between cellular ion deregulation and acute and chronic tox-icity.Toxicol. Appl. Pharmacol.97: 6–22.
191.
191. Ura H, Nowak P, Litwin S, Watts P, Bonfil RD, and Klein-Szanto AJP (1989). Effects of formaldehyde on normal xenotransplanted human tracheobron-chial epithelium.Am. J. Pathol.134: 99–106.
192.
192. Van Scott MR, Yamkaskas JR, and Boucher RC (1986). Culture of airway cells: Research techniques.Exp. Lung Res.11: 75–94.
193.
193. Vanhamme L, Rolin S, and Szpirer C (1989). In-hibitin of gap-junctional intercellular communication between epithelial cells transformed by the activated H-ras-1 oncogene.Exp. Cell Res.180: 297–301.
194.
194. Vanier MC, Danerjee D, and Mukherjce BB (1988). Retinoic acid inhibited phospholipid turnover and protein kinasc C activity in RA-sensitive but not in RA-resistant cells.FEBS. Letters241: 154–158.
195.
195. Wakefield LM, Smith DM, Masui T, Harris CC, and Sporn MB (1989). Distribution and modulation of the cellular receptor for transforming growth factor-beta in human squamous carcinoma cell lines.Cancer Res.49: 3196–3202.
196.
196. Warner AE, Guthrie SC, and Gilula NB (1984). Antibodies to gap junctional protein selectively disrupt junctional communication in the early amphibian embryo.Nature311: 127–131.
197.
197. Widdicombe JH, Coleman DL, Finkbeiner WE, and Friend DS (1987). Primary cultures of the dog's tracheal epithelium: Fine structure, fluid, and electrolyte transport.Cell Tissue Res.247: 95–103.
198.
198. Widdicombe JG (1989). Airway mucus.Eur. Resp. J.2: 107–115.
199.
199. Wiener EC and Loewenstein WR (1983). Correction of cell-cell communication defect by introduction of a protein kinase into mutant cells.Nature305: 433–435.
200.
200. Willey JC, Moser CE, Lechner JF, and Harris CC (1984). Differential effects of 12-O-tetradecanoyl-phorbol-13-acetate on cultured normal and neoplastic human bronchial epithelial cells.Cancer Res.44: 5124–5126.
201.
201. Willey JC, Saladino AJ, Ozanne C, Lechner JF, and Harris CC (1984). Acute effects of 12-O-tetradeca-noylphorbol-13-acetate, teleocidin B, 2,3,7,8-tetra-chlorodibenzo-p-dioxin on cultured normal human bronchial epithelial cells.Carcinogenesis5: 209–215.
202.
202. Willman CL and Fenoglio-Preisser CM (1987). On-cogenes, suppressor genes, and carcinogenesis.Hum. Pathol.18: 895–901.
203.
203. Wilson TS, McDowell EM, and Trump BF (1985). lmmunohistochemical studies of keratin in human bronchus and lung tumors.Arch. Pathol. Lab. Med.109: 621–628.
204.
204. Wong ST, Winchell LF, McCune BK, Earp HS, Teixido J, Massagué J, Herman B, and Lee DC (1989). The TGF-alpha precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction.Cell56: 495–506.
205.
205. World Health Organization (1982). The World Health Organization histological typing of lung tumours.Am. J. Clin. Pathol.77: 123–126.
206.
206. Woutersen RA, van Garderen-Hoetmer A, Bruijntjes JP, Zwart A, and Feron VJ (1989). Nasal tumours in rats after severe injury to the nasal mucosa and prolonged exposure to 10 ppm formaldehyde.J. Appl. Toxicol.9: 39–46.
207.
207. Wu R and Wu MM (1986). Effects of retinoids on human bronchial cells; differential regulation of hy-aluronate biosynthesis and keratin protein synthesis.J. Cell. Physiol.127: 73–82.
208.
208. Yamauchi K, Martinet Y, Basset P, Fells FA, and Crystal RG (1988). High levels of transforming growth factor-β are present in the epithelial lining fluid of the normal human lower respiratory tract.Am. Rev. Respir. Dis.137: 1360–1363.
209.
209. Yamauchi K, Basset P, Martinet Y, and Crystal RG (1987). Normal human alveolar macrophages express the gene coding for transforming growth factor-/?, a protein with the capacity to suppress fibro-blast growth.Am. Rev. Respir. Dis.135: A66.
210.
210. Yancey SB, Nicholson BJ, and Revel JP (1981). The dynamic state of liver gap junctions.J. Supramol. Struct. Cell. Biochem.16: 221–232.
211.
211. Yee AG and Revel JP (1978). Loss and reappearance of gap junctions in regenerating rat liver.J. Cell. Biol.78: 554–564.
212.
212. Yoakum GH, Lechner JF, Gabrielson EW, Korba BE, Malan-Shibley L, Willey JC, Valerio MG, Shamsuddin AM, Trump BF, and Harris CC (1985). Transformation of human bronchial epithelial cells transfected with Harvey ras oncogene.Science227: 1174–1179.
213.
213. Young JD-E, Cohn ZA, and Gilula NB (1987). Functional assembly of gap junction conductance in lipid bilayers: Demonstration that the major 27 kd protein forms the junctional channel.Cell48: 733–743.
