Neurotoxic effects of platinum compounds in cultured dorsal root ganglion cells.

Abstract

The neurotoxic cancer chemotherapeutic agent cis-diamminedichloroplatinum (II) (cis-platin) was tested in a model system of cultured embryonic chick dorsal root ganglion cells, in order to investigate cellular mechanisms of toxicity. At 7.5 ug/ml, the drug caused mild toxicity. At doses of 75 ug/ml, cis-platin was toxic to cultures in 6 hours, in both neuronal and non-neuronal cell populations. After 24 hours of incubation with 75 ug/ml cis-platin, there was extensive cell death. The trans isomer of the drug, trans-platin, was less toxic than cis-platin at similar doses, causing less severe damage to the cells as well as less cell death. With both drugs, abnormalities in patterns of nuclear staining were prominent, whereas neuronal cell membrane staining patterns were less affected. Both drugs seemed to affect non-neuronal cells to a greater extent than neurons. Ultrastructural findings with both drugs included nucleolar segregation; mitochondrial changes were nonspecific. In this in vitro system, both cis- and trans-platin are toxic. The toxicity appears to predominantly affect the nucleus, and to preferentially involve non-neuronal cells.