Changes in cellular autophagic capacity during azaserine-initiated pancreatic carcinogenesis

Growth regulation is a crucial event in tumour progression. Surprisingly, r elatively few papers have dealt with the catabolic side of regulation, and there are practically no data regarding the autophagic process during tumou r development. We approach this problem by morphometrical investigation int o the possible changes of autophagic activity during the progression of rat pancreatic adenocarcinoma induced by azaserine, In the present study, auto phagic capacity of the azaserine-induced premalignant and malignant cells w ere characterised and compared to the respective host tissue cells of the r at pancreas and to the acinar cells in other stages of turnout development. Using vinblastine (VBL) as an enhancer, and cycloheximide (CHI) as an inhi bitor of autophagic segregation we observed that autophagic capacity of pre malignant cells (month 6 and 10 after initiation) is much higher than in th e host tissue cells. We found a sharp decrease in self-digesting capacity i n adenocarcinoma cells (month 20) where VBL induced a minimal accumulation of autophagic vacuoles which was, surprisingly, not inhibited by CHI, i.e. the CHI-sensitive regulatory step was lost. The changes in autophagic capac ity are probably associated to specific steps of tumour progression in our system.