Carcinogenesis, Vol. 20, No. 10, 1893-1898,
October 1999
© 1999 Oxford University Press
Cancer Biology |
Cellular autophagic capacity is highly increased in azaserine-induced premalignant atypical acinar nodule cells
Department of General Zoology, Loránd Eötvös University, pf 330, H-1445 Budapest, Hungary
Although cellular autophagy is recognized as a major pathway of macromolecular catabolism, little data are available regarding its activity or regulation in tumor cells. We approach this problem by morphometrical investigation into the possible changes in autophagic activity during progression of rat pancreatic adenocarcinoma induced by azaserine and promoted by a raw soya flour-containing pancreatotrophic diet. In the present study, the autophagic capacity of the carcinogen-induced premalignant atypical acinar nodule cells was characterized and compared with controls (normal tissue of rats kept on standard laboratory or pancreatotrophic diet and host tissue of the premalignant nodules of the azaserine-treated rats). Given for 90 min, vinblastine, an enhancer of autophagic segregation (i.e. formation of autophagic vacuoles), caused a one to two orders of magnitude larger expansion of the autophagic compartment in atypical nodule cells than in the controls. Then a 20 min blockade of segregation by cycloheximide led to regression of the autophagic compartment, which was barely measurable or moderate in the controls but exceeded 50% in the premalignant cells. At the same time, the cytoplasmic volume fraction of early autophagic vacuoles regressed to a near zero value in each cell type. Expansion and regression rates of these nascent vacuoles showed that both segregation and degradation were 6–20 times faster in the nodule than in normal tissue cells. These results show that the autophagic capacity of the premalignant cells in our system is greatly increased, possibly making these cells unusually sensitive to up-regulation of their self-digesting activity in response to different extracellular signals or drugs.
Abbreviations: AAC, atypical acinar cell; AACN, atypical acinar cell nodule; AV, autophagic vacuole; AV1, AV2, AV3, AVc, AVt, early, advanced, late, complex and total autophagic vacuole respectively; CHI, cycloheximide; CVF, cytoplasmic volume fraction; VBL, vinblastine.
1 To whom correspondence should be addressed Email: grez{at}cerberus.elte.hu
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