Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1994 Jun;120(6):348–353. doi: 10.1007/BF01247459

Pulmonary alveolar proteinosis in rats after administration of quartz: its possible role in morphogenesis of lung cancer

J Friemann 1,✉, F Pott 2, K B Wilk 1, O Ahrens 3, M Rosenbruch 1, W Hilscher 1, H -W Schlipköter
PMCID: PMC12201285  PMID: 8138559

Abstract

In rats, primary peripheral lung tumors composed predominantly of alveolar type II cells have been induced by inhalation of α quartz. In our retrospective study on proliferation markers we evaluated lung specimens of 140 Wistar rats from larger experiments, which had been exposed to Dörentrup quartz (DQ12) by inhalation (10 mg/m3, 56 Weeks, 5 days/week, 7 h/day:n=27) or intratracheal instillations (5 mg:n=38; 20 mg:n=10; 50 mg:n=28; 15×3 mg:n=12). In the last group 8/12 animals developed lung tumors. Animals were sacrificed 1–32 months after administration. For identification of an increased proliferation of alveolar type II cells the DNA content was monitored by microscopic (static) cytophotometry in histological slides. The argyrophil (AgNOR) method for the demonstration of nucleolar organizer regions (NOR) was used as second marker of type II cell proliferation. Measurements made 24 months after inhalation of DQ12 showed a slight increase of pneumocytic proliferation with 1.64±0.14 AgNOR/nucleus compared to the controls (1.23±0.04 mean AgNOR/nucleus). After intratracheal instillation of DQ12 a significant increase of AgNOR was found, e.g. 5 mg: 1.93±0.23 AgNOR/nucleus (6 months) and 1.96±0.19 (12 months); 50 mg: 1.77±0.15 (6 months) and 2.18±0.05 (12 months); 15×3 mg (+2 ml 2% polyvinylpyridineN-oxide s.c.): 1.81±0.13 AgNOR/nucleus (27–32 months). With the aid of the 2c deviation index, i.e. the mean square deviation from the diploid DNA value, it was possible also to identify the pathologically increased proliferation of type II cells after intratracheal instillation of quartz: 0.02±0.01−0.06±0.04c 2 (controls); 0.07±0.04c 2 (5 mg/12 months); 0.12±0.08c 2 (15×3 mg/>27 months) and 0.68±0.48c 2 (50 mg/12 months). Only in the last group were nearly triploid values detected. Summarizing our results, intratracheal instillation and inhalation of quartz in rats regularly induces alveolar proteinosis and interstitial fibrosis in combination with a dose- and time-dependent increase of the type II cell proliferation rate. As mitogenesis increases carcinogenesis, alveolar proteinosis with increased pneumocytic proliferative activity might be a prerequisite for enhanced tumor development.

Key words: Pulmonary alveolar proteinosis, Quartz as carcinogen, Lung cancer, Morphogenesis of cancer

References

  1. Ames BN, Gold LS (1990) Too many rodent carcinogens: mitogenesis increases mutagenesis. Science 249:970–971 [DOI] [PubMed] [Google Scholar]
  2. Ames PG, Amandus H, Attfield M, Green FY, Vallyathan V (1983) Does coal mine dust present a risk for lung cancer? A case-control study of US coal miners. Arch Environ Health 38:331–333 [DOI] [PubMed] [Google Scholar]
  3. Banks DE (1986) Acute silicosis. DHHS NIOSH publication, 86–102:239–241 [Google Scholar]
  4. Bocking A, Adler C-P, Common HH, Hilgarth M, Granzen B, Auffermann W (1984) Algorithm for a DNA-cytophotometric diagnosis and grading of malignancy. Anal Quant Cytol 6:1–8 [PubMed] [Google Scholar]
  5. Büchner HA, Ansari A (1969) Acute silico-proteinosis. A new pathologic variant of acute silicosis in sandblasters, characterized by histologic features resembling alveolar proteinosis. Dis Chest 55:274–284 [DOI] [PubMed] [Google Scholar]
  6. Cohen SM, Ellwein LB (1990) Cell proliferation in carcinogenesis. Science 249:1007–1011 [DOI] [PubMed] [Google Scholar]
  7. Craighead JE (1992) Do silica and asbestos cause lung cancer? Arch Pathol Lab Med 116S:16–20 [PubMed] [Google Scholar]
  8. Feulgen R, Rossenbeck H (1924) Mikroskopisch-chemischer Nachweis einer Nucleinsäure vom Typus der Thymonucleinsäure und die darauf beruhende selektive Färbung von Zellkernen in mikroskopischen Präparaten. Z Physiol Chem 135:203–248 [Google Scholar]
  9. Goessens G, Thiry M, Lepoint A (1987) Relations between nucleoli and nucleolus-organizing regions during the cell cycle. In: Stahl A, Lucini JM, Vagner-Capodano AM (eds) Chromosomes today. 9. Allen & Unwin, London, pp 261–271 [Google Scholar]
  10. Graumann W (1953) Zur Standardisierung des Schiffschen Reagens. Z Wiss Mikrosk Mikrosk Tech 61:225–226 [Google Scholar]
  11. Groth DH, Stettler LE, Platek SF, Lal JB, Burg JR (1986) Lung tumors in rats treated with quartz by intratracheal instillation. In: Goldsmith DF, Winn DM, Stiy CM (eds) Silica Silicosis Cancer 24:243–253
  12. Grundmann E, Hillmans HG, Rha K (1961) Cytofotometrische Untersuchungen am menschlichen Portioepithel während der Krebsentwicklung. Z Krebsforsch 64:390–40213902439 [Google Scholar]
  13. Hilscher W, Rosmanith J, Thome E, Koep D (1991) Morphometrische Untersuchungen an den Lungen und Lymphknoten von Ratten nach intratrachealer Instillation quarzhaltiger Stäube zur Erfassung der minimalen Dosis. In: Ergeb Untersuch Geb Staub Silikosebekämpfung: Steinkohlenbergbau Silikosebericht NRW 18:223–238
  14. Hnizdo E, Sluis-Cremer GK (1991) Silica exposure, silicosis, and lung cancer: a mortality study of South African gold miners. Br J Ind Med 48:53–60 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hoffmann EO, Lamberty J, Pizzolato P, Coover J (1973) The ultrastructure of acute silicosis. Arch Pathol 96:104–107 [PubMed] [Google Scholar]
  16. Holland LM, Gonzales M, Wilson JS, Tillery MI (1983) Pulmonary effects of shale dusts in experimental animals. In: Wagner WL, Rom WN, Merchant JA (eds) Health issues released to metal and nonmetallic mining. Butterworth, Boston, pp 485–496 [Google Scholar]
  17. Holland LM, Wilson JS, Tillery MI, Smith DM (1986) Lung cancer in rats exposed to fibrogenic dusts. In: Goldsmith DF, Winn DM, Shy CM (eds) Silica, silicosis cancer. Praeger, New York, pp 267–279 [Google Scholar]
  18. Johnson NF, Smith DM, Sebring R, Holland LM (1987) Silica-induced alveolar cell tumors in rats. Am J Ind Med 11:93–107 [DOI] [PubMed] [Google Scholar]
  19. Kawada H, Horiuchi T, Shannon JM, Kuroki Y, Voelker DR, Mason RG (1989) Alveolar type II cells, surfactant protein A (SP-A), and the phospholipid components of surfactant in acute silicois in the rat. Am Rev Respir Dis 140:460–470 [DOI] [PubMed] [Google Scholar]
  20. Kissler W (1983) Formal genesis of pulmonary fibrosis: experimental investigations. In: Müller K-M (ed) Pulmonary diseases-clinicopathological correlations. Springer, New York Heidelberg Tokyo, pp 207–231 [DOI] [PubMed] [Google Scholar]
  21. Mellin W (1990) Cytophotometry in tumor pathology. A critical review of methods and applications, and some results of DNA analysis. Pathol Res Pract 186:37–62 [DOI] [PubMed] [Google Scholar]
  22. Merlo F, Doria M, Fontana L, Ceppi M, Chesi E, Santi L (1990) Mortality from specific causes among silicotic subjects: a historical prospective study. In: Simonato L, Fletcher AC, Saracchi R, Thomas TL (eds) Occupational exposure to silica and cancer risk. pp 105–115 [PubMed]
  23. Miller BG, Jacobsen M (1985) Dust exposure, pneumoconiosis, and mortality of coalminers. Br J Ind Med 42:723–733 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Morton CC, Brown JA, Holmes WM, Nance WE, Wolf B (1983) Stain intensity of human nucleolus organiser region reflects incorporation of uridine into mature ribosomal RNA. Exp Cell Res 145:405–413 [DOI] [PubMed] [Google Scholar]
  25. Muhle H, Takenaka S, Mohr U, Dasenbrock C, Mermel-Stein R (1989) Lung tumor induction upon long-term low-level inhalation of crystalline silica. Am J Ind Med 15:343–346 [DOI] [PubMed] [Google Scholar]
  26. OSTP (Office of Science and Technology Policy) (1985) Guidelines on assessing chemical carcinogens (50 FR 10372, March 14, 1985). A review of the science and its associated principles. Chapter 3. Long-term carcinogen bioassay. Bureau of national affairs. Washington, DC, pp 2040–2049 [Google Scholar]
  27. Pairon JC, Brochard P, Jaurand MC, Bignon J (1991) Silica and lung cancer: a controversial issue. Eur Respir J 4:730–744 [PubMed] [Google Scholar]
  28. Pott F, Dungworth DL, Heinrich U, Muhle H, Kamino K, Germann P-G, Roller M, Rippe R-M, Mohr U (1991) Lung tumours in rats after intratracheal instillation of dusts. British Occupational Hygiene Society, 7th Symposium on inhaled particles Edinburgh, 16–20, September 1991. Ann Occup Hyg [Suppl] (in press)
  29. Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE (1990) Increased cell division as a cause of human cancer. Cancer Res 50:7415–7421 [PubMed] [Google Scholar]
  30. Reeves BR, Casey G, Honeycomb JR, Smith S (1984) Correlation of differentiation state and silver staining of nucleolar organizers in the promyelocytic leukaemia cell line HL-60. Cancer Genet Cytogenet 13:159–199 [DOI] [PubMed] [Google Scholar]
  31. Reitemeyer E, Böhm E, Müller K-M (1985) Silikose und Bronchialkarzinom: Pathologische Anatomie und gutachterliche Problematik. Prax Klin Pneumol 39:679–680 [Google Scholar]
  32. Rosenbruch M, Idel H, Friedrichs KH, Reiffer FJ, Brockhaus A (1990) Vergleichende Untersuchungen zur Wirkung von Quarzglas und Quarz DQ-12 im Inhalationsversuch bei Ratten. Zbl Hyg 189:419–440 [PubMed] [Google Scholar]
  33. Rüschoff J Barth P (1992) Theorie und Praxis der Silberfärbung Nukleolus organisierender Regionen (AgNOR). Der Pathologe 13:13–19 [PubMed] [Google Scholar]
  34. Saeter G, Schwarze PE, Seglen PO (1988) Shift from polyploidizing to nonpolyploidizing growth in carcinogen treated rat liver. J Natl Cancer Inst 80:950–958 [DOI] [PubMed] [Google Scholar]
  35. Sargent L, XU YH, Sattler GL, Meisner L, Pitot HC (1989) Ploidy and karyotype of hepatocytes isolated from enzyme altered foci in two different protocols of multistage hepatogenesis in the rat. Carcinogenesis 10:387–391 [DOI] [PubMed] [Google Scholar]
  36. Simonato L, Saracci R (1990) Epidemiological aspects of the relationship between exposure to silica dust and lung cancer. In: Simonato L, Fletcher AC, Saracci R, Thomas TL (eds) Occup Exp Silica Cancer Risk. IARC, Lyon, pp 1–5 [PubMed] [Google Scholar]
  37. Suratt PM, Washington CW, Brody AR, Bolton WK, Giles RD (1977) Acute silicosis in tombstone sandblasters. Am Rev Respir Dis 115:521–529 [DOI] [PubMed] [Google Scholar]
  38. Weller W (1977) Anthrakosilikose. Tierexperimentelle Forschung. Bergbau-Berufsgenossenschaft, Silikoseforschungsinstitut Bochum, p 320
  39. Zimmermann PV, Sinclair RA (1988) Rapidly progressive fatal silicosis in young man. Med J Aust 704–706 [DOI] [PubMed]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES