Nuclear and nucleolar damage in adriamycin-induced toxicity to rat sensory ganglion cells.

A single dose (10 mg/kg) of Adriamycin was given to 23 adult Wistar rats and the spinal ganglia were studied from 6 h to 15 days after. As previously described, this drug results in the appearance of 'clear' areas in the nuclei of rat spinal ganglion cells as seen by light and by electron microscopy. The 'clear' areas become less conspicuous during the week before the onset of cytoplasmic degeneration. In addition, nucleolar changes become increasingly evident with time after injection. Fibrillar centres enlarge and nucleolar segregation is present from 24 h onwards, although the latter is invariably partial and more readily seen with the electron microscope. Nucleolar fragmentation is seen more frequently from 3 days onwards and nucleolar enlargement is common from 6 days. Early cytoplasmic abnormalities are associated with pronounced loss of Nissl substance. Adriamycin must bind extensively to nuclear DNA in spinal ganglion cells, causing the 'cleared' nuclear areas and the changes in dense chromatin. In addition, the binding of Adriamycin to nucleolar DNA with disturbance to nucleolar functions must be important in producing later cytoplasmic changes that precede cell death. There are thus similarities between the action of Adriamycin on these cells and those of Cisplatin, although in the latter intoxication the nuclear effects are significantly less prominent.