Role of platinum DNA damage-induced transcriptional inhibition in chemotherapy-induced neuronal atrophy and peripheral neurotoxicity

摘要: Platinum-based anticancer drugs cause peripheral neurotoxicity by damaging sensory neurons within the dorsal root ganglia (DRG), but mechanisms are incompletely understood. The roles of platinum DNA binding, transcription inhibition and altered cell size were investigated in primary cultures rat DRG cells. Click chemistry quantitative fluorescence imaging RNA-incorporated 5-ethynyluridine showed high, wide ranging, global levels individual that correlated with their body size. Treatment reduced neuronal to an extent corresponded amount preceding without any loss effects on inhibited blocking binding sodium thiosulfate, mimicked treatment a model transcriptional inhibitor, actinomycin D. In vivo oxaliplatin depleted total RNA content tissue concurrently altering These findings point mechanism chemotherapy-induced neurotoxicity, whereby damage induces arrest leading turn atrophy. may be particularly vulnerable this toxicity because requirements for high basal activity. Findings new stepwise Dorsal ganglion outputs, demonstrated study click imaging.