View More View Less
  • 1 Department of General Zoology, Eötvös Loránd University, Please ask the editor of the journal.
  • 2 Department of Botany and Plant Physiology, Szent István University, H-2103 Gödöllő, Páter K. út 1, Hungary
  • 3 Department of General Zoology, Eötvös Loránd University, Please ask the editor of the journal.
  • 4 Department of General Zoology, Eötvös Loránd University, Please ask the editor of the journal.
Restricted access

Growth regulation is a crucial event in tumour progression. Surprisingly, relatively few papers have dealt with the catabolic side of regulation, and there are practically no data regarding the autophagic process during tumour development. We approach this problem by morphometrical investigation into the possi- ble changes of autophagic activity during the progression of rat pancreatic adenocarcinoma induced by azaserine. In the present study, autophagic capacity of the azaserine-induced premalignant and malignant cells were characterised and compared to the respective host tissue cells of the rat pancreas and to the acinar cells in other stages of tumour development. Using vinblastine (VBL) as an enhancer, and cyclo- heximide (CHI) as an inhibitor of autophagic segregation we observed that autophagic capacity of pre- malignant cells (month 6 and 10 after initiation) is much higher than in the host tissue cells. We found a sharp decrease in self-digesting capacity in adenocarcinoma cells (month 20) where VBL induced a min- imal accumulation of autophagic vacuoles which was, surprisingly, not inhibited by CHI, i.e. the CHI- sensitive regulatory step was lost. The changes in autophagic capacity are probably associated to specif- ic steps of tumour progression in our system.

  • Seglen, P. O. (1997) DNA ploidy and autophagic protein degradation as determinants of hepatocellular growth and survival. Cell Biol. Toxicol. 13, 301-315.

    'DNA ploidy and autophagic protein degradation as determinants of hepatocellular growth and survival ' () 13 Cell Biol. Toxicol. : 31 -315.

    • Search Google Scholar
  • Tessitore, L., Bonelli, G., Cecchini, G., Amenta, J. S., Baccino, F. M. (1987) Regulation of protein turnover versus growth state: ascites hepatoma as a model for studies both in the animal and in vitro. Arch. Biochem. Biophys. 255, 372-384.

    'Regulation of protein turnover versus growth state: ascites hepatoma as a model for studies both in the animal and in vitro ' () 255 Arch. Biochem. Biophys. : 31 -384.

    • Search Google Scholar
  • Weibel, E. R. (1969) Stereological principles for morphometry in electron microscopic cytology. Int. Rev. Cytol., 26, 235-302.

    'Stereological principles for morphometry in electron microscopic cytology ' () 26 Int. Rev. Cytol. : 31 -302.

    • Search Google Scholar
  • Yager, J. D., Roebuck, B. D., Zurlo, J., Longnecker, D. S., Weselcouch, E. O., Wilpone, S. A. (1981) A single-dose protocol for azaserine initiation of pancreatic carcinogenesis in the rat. Int. J. Cancer 28, 601-606.

    'A single-dose protocol for azaserine initiation of pancreatic carcinogenesis in the rat ' () 28 Int. J. Cancer : 31 -606.

    • Search Google Scholar
  • Longnecker, D. S. (1986) Experimental models of exocrine pancreatic tumors. In: Go, V. L. W., Gardner, J. D., Brooks, F. P., Lebenthal, E., Di Magno, E. P., Scheele, G. A. (eds) The exocrine pancreas biology, pathobiology and diseases. Raven Press, New York. pp. 443-458.

    The exocrine pancreas biology, pathobiology and diseases , () 443 -458.

  • Oliva, O., László, L., Pálfia, Z., Réz, G. (1991) Translational inhibitors cycloheximide, emetin and puromycin inhibit cellular autophagy in mouse liver parenchymal and pancreatic acinar cells in vivo. Acta Morphologica Hung. 39(2), 79-85.

    'Translational inhibitors cycloheximide, emetin and puromycin inhibit cellular autophagy in mouse liver parenchymal and pancreatic acinar cells in vivo ' () 39 Acta Morphologica Hung. : 31 -85.

    • Search Google Scholar
  • Kisen, G. X., Tessitore, L., Costelli, P., Gordon, P. B., Schwarze, P. E., Baccino, F. M., Seglen, P. O. (1993) Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells. Carcinogenesis 14(2), 2501-2505.

    'Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells ' () 14 Carcinogenesis : 31 -2505.

    • Search Google Scholar
  • Longnecker, D. S., Roebuck, B. D., Yager, J. D., Lilja, H. S., Sigmund, B. (1981) Pancreatic carcinoma in azaserine-treated rats (induction, classification and dietary modulation of incidence). Cancer 47, 1562-1572.

    'Pancreatic carcinoma in azaserine-treated rats (induction, classification and dietary modulation of incidence) ' () 47 Cancer : 31 -1572.

    • Search Google Scholar
  • Farguhar, M. G. (1969) Lysosome function in regulating secretion: disposal of secretory granules in cells of the anterior pituitary gland. In: Dingle, J. T., Fell, H. B. (eds) Lysosomes in biology and pathology. North-Holland Publ. Co., Amsterdam-London, Vol. 2, pp. 462-482.

    Lysosomes in biology and pathology , () 462 -482.

  • Gunn, J. M., Clank, M. G., Knowles, S. E., Hopgood, M. F., Ballard, F. J. (1977) Reduced rates of proteolysis in transformed cells. Nature 266, 58-60.

    'Reduced rates of proteolysis in transformed cells ' () 266 Nature : 31 -60.

  • Kovács, J. (1983) Regression of autophagic vacuoles in seminal vesicle cells following cycloheximide treatment. Exp. Cell Res. 144, 231-234.

    'Regression of autophagic vacuoles in seminal vesicle cells following cycloheximide treatment ' () 144 Exp. Cell Res. : 31 -234.

    • Search Google Scholar
  • Papadopoulos, T., Pfeifer, U. (1986) Regression of rat liver autophagic vacuoles by locally applied cycloheximide. Lab. Invest. 54, 100-107.

    'Regression of rat liver autophagic vacuoles by locally applied cycloheximide ' () 54 Lab. Invest. : 31 -107.

    • Search Google Scholar
  • Pfeifer, U. (1987) Functional morphology of the lysosomal apparatus. In: Glaumann, H., Ballard, F. J. (eds) Lysosomes, their role in protein breakdown. Academic Press, London, UK, pp. 3-59.

    Lysosomes, their role in protein breakdown , () 3 -59.

  • Pfeifer, U., Tessitore, L., Bonelli, G., Baccino, F. M. (1988) Regulation of protein turnover versus growth state III. Growth cessation is associated with activation of autophagy in Yoshida ascites hepatoma AH-130. Virchows Arch. B Cell Pathol. 55, 3763-3769.

    'Regulation of protein turnover versus growth state III. Growth cessation is associated with activation of autophagy in Yoshida ascites hepatoma AH-130 ' () 55 Virchows Arch. B Cell Pathol. : 31 -3769.

    • Search Google Scholar
  • Punnonen, E. L., Reunanen, H. (1990) Effects of vinblastine, leucine, and histidine, and 3-methyladenine on autophagy in Ehrlich ascites cells. Exp. Mol. Pathol. 52, 87-97.

    'Effects of vinblastine, leucine, and histidine, and 3-methyladenine on autophagy in Ehrlich ascites cells ' () 52 Exp. Mol. Pathol. : 31 -97.

    • Search Google Scholar
  • Réz, G., Tóth, S., Pálfia, Z. (1999) Cellular autophagic capacity is highly increased in azaserine-induced premalignant atypical acinar nodule cells. Carcinogenesis 20, 1893-1898.

    'Cellular autophagic capacity is highly increased in azaserine-induced premalignant atypical acinar nodule cells ' () 20 Carcinogenesis : 31 -1898.

    • Search Google Scholar
  • Réz, G., Csák, J., Fellinger, E., László, L., Kovács, A. L., Oliva, O., Kovács, J. (1996) Time course of vinblastine-induced autophagocytosis and changes in the endoplasmic reticulum in murine pancreatic acinar cells: a morphometrical and biochemical study. Eur. J. Cell Biol. 71, 341-350.

    'Time course of vinblastine-induced autophagocytosis and changes in the endoplasmic reticulum in murine pancreatic acinar cells: a morphometrical and biochemical study ' () 71 Eur. J. Cell Biol. : 31 -350.

    • Search Google Scholar
  • Schulte-Hermann, R., Bursch, W., Grasl-Kraupp, B., Torok, L., Ellinger, A., Mullauer, L. (1995) Role of active cell death (apoptosis) in multi-stage carcinogenesis. Toxicol. Lett. 82-83, 143-148.

    'Role of active cell death (apoptosis) in multi-stage carcinogenesis ' () 82-83 Toxicol. Lett. : 31 -148.

    • Search Google Scholar
  • Baccino, F. M., Tessitore, L., Bonelli, G. (1984) Control of protein degradation and growth phase in normal and neoplastic cells. Toxicol. Pathol. 12, 281-287.

    'Control of protein degradation and growth phase in normal and neoplastic cells ' () 12 Toxicol. Pathol. : 31 -287.

    • Search Google Scholar
  • Boyer, M. J., Tannock, I. F. (1993) Lysosomes, lysosomal enzymes and cancer. Adv. Canc. Res. 60, 269-291.

    'Lysosomes, lysosomal enzymes and cancer ' () 60 Adv. Canc. Res. : 31 -291.

  • Bursch, W., Ellinger, A., Kienzl, H., Török, L., Pandey, S., Sikorska, M. Walker, R., Hermann, R. S. (1996) Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 17, 1595-1607.

    'Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy ' () 17 Carcinogenesis : 31 -1607.

    • Search Google Scholar
  • Ahlberg, J., Yucel, T., Eriksson, L., Glaumann, H. (1987) Characterization of the proteolytic compartment in rat hepatocyte nodules. Virchows Arch. B. Cell Path. 53, 79-88.

    'Characterization of the proteolytic compartment in rat hepatocyte nodules ' () 53 Virchows Arch. B. Cell Path. : 31 -88.

    • Search Google Scholar
  • Oliva, O., Réz, G., Pálfia, Z., Fellinger, E. (1992) Dynamics of vinblastine-induced autophagocytosis in murine pancreatic acinar cells: influence of cycloheximide post-treatments. Exp. Molec. Pathol. 56, 76-86.

    'Dynamics of vinblastine-induced autophagocytosis in murine pancreatic acinar cells: influence of cycloheximide post-treatments ' () 56 Exp. Molec. Pathol. : 31 -86.

    • Search Google Scholar
  • Schwarze, P. E., Seglen, P. O. (1985) Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats. Exp. Cell Res. 157, 15-28.

    'Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats ' () 157 Exp. Cell Res. : 31 -28.

    • Search Google Scholar
  • Seglen, P. O., Schwarze, P. E., Saeter, G. (1986) Changes in cellular ploidy and autophagic responsiveness during rat liver carcinogenesis. Toxicol. Pathol., 14, 342-348.

    'Changes in cellular ploidy and autophagic responsiveness during rat liver carcinogenesis ' () 14 Toxicol. Pathol. : 31 -348.

    • Search Google Scholar