Alteration of ganglioside composition and metabolism in doxorubicin-resistant rat tumoral cells

Abstract

We have investigated the ganglioside levels, composition and metabolism in two lines of doxorubicin-resistant cells and in the corresponding wild strains, the C6 rat glioblastoma and the HTC rat hepatoma. The only ganglioside present was G M3, and its level was increased 2-fold in C6 resistant cells and decreased nearly 2-fold in HTC resistant cells. A decrease of cytidine 5'-monophospho- N-acetylneuraminic acid: galactosylglucosylceramide sialyltransferase activity was observed in both resistant lines as compared to sensitive ones, and could not, therefore, explain the increase in the G M3 level observed in the C6 resistant line. Alterations of acid neuraminidase activity were also observed; a 5-fold decrease was noticed in the C6 resistant line and could account for the increase in the G M3 level observed in these cells; in contrast, a 2-fold increase of acid neuraminidase activity was noticed in the HTC resistant cells: together, with reduced synthesis, it could explain the decrease in the G M3 level observed in these cells. No alteration of exogenous ganglioside transport was exhibited by the C6 resistant cells.