THE CELLULAR TOXICITY OF 2 ANTITUMORAL AGENTS DERIVED FROM PLATINUM, CISPLATINUM VERSUS OXALIPLATINUM, ON CULTURES OF TUBULAR PROXIMAL CELLS

There is a large scope for the use for cisplatin and its derivatives i n the treatment of human malignancies. Nephrotoxicity is their most im portant use-limiting factor. The aim of this study has been to compare cisplatin (CDDP) and oxaliplatin (1-OHP), a new derivative, on cultur es of tubular proximal cells. Three cells models were used: primary cu lture of rabbit kidney, proximal tubular cells (RPTC) and established opossum kidney (OK) and pig kidney (LLC-PK1) epithelial cell lines. Re sults indicate that in these three culture systems, the cytotoxicity-r anking of the two molecules were in agreement with their in vivo nephr otoxicity (CDDP > 1-OHP), but were less cytotoxic for OK and LLC-PK1 c ells than for RPTC. Functional and biochemical evaluations in RPTC ind icate that toxic effects of platinum derivates are exerted on DNA, pro tein synthesis and glucose uptake. 1-OHP effect on DNA synthesis seems to be more effective, but induced a more progressive cytotoxicity. Al teration of glutathione-dependent detoxication activities may reflect the occurrence of a lipid peroxidation process. The present study show ed that 1) RPTC are more suitable that LLC-PK1 or OK cells for investi gating the nephrotoxicity of platinum derivatives; 2) 1-OHP seems to h ave a more powerful pharmacological effect than CDDP. The toxic effect ratio seems to promise greater safety with 1-OHP than with CDDP.