TOXIC EFFECTS OF 2 ANTINEOPLASTIC AGENTS DERIVED FROM PLATINUM, THE CIS-DIAMMINO-DICHLORO-PLATINUM (II) AND THE TRANS-1,2-DIAMMINO-CYCLO-HEXANE-PLATINUM (II), ON PRIMARY CULTURES OF RABBIT PROXIMAL TUBULAR CELLS

There is a large field of use for cisplatin and its derivatives in the treatment of human malignancies. The nephrotoxicity is their most imp ortant use-limiting factor. The aim of this work has been to study com paratively the cisplatin and a new molecule , the oxaliplatin on prima ry culture of proximal tubular cells of rabbit kidney. Several markers , functional enzymatic and biochemical have been evaluated after expos ure to platinum's derivatives. The results indicates that their toxic effects are exerted on DNA and proteins synthesis, and for the cisplat in on the glucose uptake. Oxalyplatin's effect on DNA synthesis seems to be more effective , but induced a more progressive cytotoxicity. Th e lipids peroxydation's role with abnormalities of glutathione dependa nt detoxication system of the cell is possible. In conclusion,oxalipla tin seems to have a pharmacological effect more powerful than cisplati n. Its low dose effect ratio seems to promise greater safety in its us e.