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Subcellular Localization of Surface Adenosine Triphosphatase Activity in Preneoplastic Liver Parenchyma¹

Laboratoires de Recherche, Institut du Cancer de Montréal, Hôpital Notre-Dame, and Département d'Anatomie, Université de Montréal, Montréal, Canada

The distribution of surface ATPase activity in hepatocytes of rats fed N,N'-dimethylaminoazobenzene was studied with the electron microscope. Enzyme activity was demonstrated by the Wachstein-Meisel technique applied to sections of glutaraldehyde-fixed tissues. Hepatocytes of N,N'-dimethylaminoazobenzene-induced regenerative nodules showed a distribution of ATPase activity similar to that observed in normal liver: the activity was present at the surface membranes limiting the bile canaliculi and not at the apposed lateral membranes. On the other hand, hyperbasophilic foci arising from the nodules exhibited activity over the entire surface of hepatocytes, rather than only at the bile canaliculi. The altered pattern of surface ATPase activity was discernible even in well-differentiated hepatocytes within the foci. The surface changes were followed by an increased irregularity of the plasma membranes and alterations of other cell organelles, suggestive of dedifferentiation. ATPase activity was also present on the entire surface of hepatoma cells in N,N'-dimethylaminoazobenzene-induced tumors, although the variable response of neoplastic membranes depended upon different cell types. It seems that the changes in distribution of surface ATPase activity are associated with early events of neoplastic development in hyperbasophilic foci.

¹ This work was supported by grants from the National Cancer Institute of Canada, and also by grants from La Fondation J. Biermans and Les Fondations J. Rhéaume.

² Research Associate of the National Cancer Institute of Canada.

Received 12/13/71. Accepted 4/26/72.