Gamma-glutamyltransferase (GGT)
hydrolyses gamma-glutamylated peptides, including
glutathione and transports amino acids into the cells. The
enzyme is up-regulated in some tumors, especially those
with a higher degree of malignancy and resistance to
cytostatics. In this study we examined the effects of
Cisplatin (1.6 x 10-5M) on the activity of GGT in
astrocytic C6 glioma cells in cultures monitored for
growth, morphology and differentiation. Initially (24 h),
the drug inhibited cell division and later (96 h), it caused
apoptotic death of about half of the population. The
more resistant and surviving cells became hypertrophic
and more differentiated, as indicated by their larger size
and higher protein content, including the maturationspecific
GFAP. In addition, the activity of GGT was
significantly elevated in these cells at 48 h and onwards.
At 96 h, the biochemically determined enzyme activity
was between 230% and 330% above the controls.
Compared to the protein content, the GGT activity
started to increase later (48 h) but it grew steeper
towards 72-96 h. Similarly, histochemical analysis
revealed a manifold increase in the number of GGT+
cells in the population and higher intensity of staining
per cell from at 48 h and onwards. The study showed
that the transformed astrocytic cells can up-regulate
GGT activity as part of an adaptation and/or, survivalenhancing
reaction triggered by Cisplatin