AN ULTRASTRUCTURAL-STUDY OF NEURONAL CHANGES IN DORSAL-ROOT GANGLIA (DRG) OF RATS AFTER CHRONIC CISPLATIN ADMINISTRATIONS

In humans, the main dose-limiting side-effect of cisplatin (CDDP) trea tment is a peripheral sensory neuropathy secondary to dorsal root gang lion (DRG) neuron involvement. To investigate further for neuronal alt erations responsible for CDDP neurotoxicity we undertook the present e xperimental ultrastructural study, based on observations of 3 differen t groups of rats (6 animals in each group). Group A rats were treated with 1 mg/kg weekly for 9 weeks; Group B with 2 mg/kg weekly for 9 wee ks; and group C rats served as untreated controls. At the end of the e xperiment, rats were perfused with 3% glutaraldehyde and lumbar DRGs w ere prepared for electron microscopic observations. In CDDP-treated ra ts somatic, nuclear and, above all, nucleolar size was reduced. Ultras tructurally, the nucleolus was the most affected structure. Nucleolar alterations were quantified morphometrically. Less marked changes were seen in the nucleus and in the RER and Golgi apparatus of the cytopla sm. The number of lysosomes and lipofuscins was greatly increased in C DDP-treated rats. The ultrastructural alterations observed in CDDP rat s suggest that CDDP may be neurotoxic due to a reduction in protein sy nthesis. This assumption would explain why cells such as neurons, whic h are non replicating, but which have a high rate of protein synthesis , may be the target of the neurotoxic action of CDDP. The lack of an e fficient blood/nerve barrier in the DRG explains the involvement of th is particular type of neuron.