CHANGES IN CELLULAR AUTOPHAGIC CAPACITY DURING AZASERINE-INITIATED PANCREATIC CARCINOGENESIS

Nagy, Krisztina and Tóth, S. and Pálfia, Z. and Réz, G. (2001) CHANGES IN CELLULAR AUTOPHAGIC CAPACITY DURING AZASERINE-INITIATED PANCREATIC CARCINOGENESIS. Acta Biologica Hungarica, 52 (4). pp. 393-401. ISSN 0236-5383

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Abstract

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.

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