INTRAVESICAL CHEMOTHERAPY WITH GAMMA-LINOLENIC ACID BECOMES A REALISTIC PROSPECT IN SERUM-FREE APPLICATIONS - IN-VITRO CYTOTOXICITY AND SYSTEMIC ABSORPTION STUDIES

Purpose: To assess the cytotoxicity of Meglumine gamma linolenic acid (MeGLA) in serum-free application on 2 urothelial cancer cell lines, t o examine whether the instant kill action of MeGLA is retained in a se rum free environment, and to study the pharmacokinetics of intravesica l instillation of gamma Linolenic acid (GLA). Materials and Methods: T he 2 human urothelial cancer cell lines (MGH-U1 & RT112) were utilized in classical cytotoxicity assays in which drug exposure lasted 2 hour s in serum or in serum-free application. The thiozolyl blue (MTT) assa y was used to quantify the residual viable biomass 5 days later. Immed iate cytotoxicity was also compared in serum and serum-free applicatio n. Four Wistar rats were used to study the intravesical absorption pro file of tritiated GLA (H-3-GLA). Results: There was a 10-fold enhancem ent of the lytic efficacy of MeGLA in serum-free application and this enhancement was also observed in experiments assessing instant kill. T here was a similar enhancement of efficacy seen in the multi-drug resi stant (MDR) clone of cells. The absorption profile showed < 2% of inst illed counts were absorbed and the commonest destination for the absor bed CLA was the Liver. Conclusions: The cytotoxic action of MeGLA was enhanced in serum free application. This enhancement was maintained wh en cells expressed the MDR phenotype. There was limited absorption fro m the bladder. MeGLA is a feasible intravesical agent for use in super ficial bladder cancer.