NEUROTOXIC EFFECT OF CISPLATIN AND THE CISPLATIN-PROCAINE COMPLEX DPRSTUDIED IN ORGANOTYPIC CULTURES OF CHICK EMBRYONIC DORSAL-ROOT GANGLIA

Neurotoxic effects of cisplatin and the cisplatin-procaine complex cis -diaminechloro-[2-(diethylamino)ethyl 4-aminobenzoate, N4]-chloridepla tinum(II) monohydrochloride monohydrate (DPR) were compared in organot ypic cultures of chick embryonic dorsal root ganglia maintained in a s emi-solid (soft agar) culture medium. The changes of two characteristi cs of the neurite outgrowth, the mean radial length of neuritic proces ses growing out from the ganglia and the area of neurite outgrowth aro und the ganglion, were used as parameters to evaluate the toxic effect of both compounds. The drugs were administered to the cultures at con centrations ranging from 13 to 120 mu M. The half-maximum inhibition c oncentration (IC50) was determined from the concentration-response cur ves for both the mean radial length of neurites and the area of neurit e outgrowth. An analysis of these parameters revealed that DPR was sig nificantly less neurotoxic than cisplatin. In fact, considering the me an radial length of neurite processes, the IC(50)s of cisplatin were 5 6, 65 and 66 mu M after 24, 48 and 72 h of exposure, respectively. By contrast, for DPR the IC(50)s were 116 mu M after 24 h, and greater th an 120 mu M after 48 and 72 h of exposure. When we considered the area index (i.e. the area of neurite outgrowth normalized for the area of the ganglia), the IC(50)s for cisplatin were 41, 52 and 55 mu M after 24, 48 and 72 h of exposure, respectively, whereas for DPR the IC(50)s were 59 mu M after 24 h, and greater than 120 mu M after 48 and 72 h of exposure. Our results support previous findings of lower toxicity o f DPR to non-neoplastic tissues, as compared to cisplatin. [(C) 1998 L ippincott Williams & Wilkins.].