Selective cytoplasmic and membrane changes induced by cisplatinum

Cisplatinum (cis-dichlorodiammineplatinum II (NSC-119875], proven to be of therapeutic value in a variety of solid tumors, is thought to have DNA as its major target. Prior in vitro studies have suggested that it also induced cell membrane and cytoplasmic changes. To better understand glial tumor cell sensitivity to cisplatinum and to design more effective adjuvant therapy, three cisplatinum sensitive human glioma-derived cell lines, SNB-1, SNB-3, SNB-4, were examined by transmission electron microscopy for cisplatinum induced changes. Tumor cells were exposed to 25, 50, and 100 micrograms/ml cisplatinum in medium for varying time periods (4-72 hours). Four changes were consistent: cell rounding and reduced nuclear-cytoplasmic ratio, nuclear chromatin clumping, vesiculation and swelling of the golgi apparatus, and dilatation of the smooth endoplasmic reticulum. These morphologic changes are distinct for cisplatinum and unlike those induced by BCNU (plasma membrane blebbing) and AZQ (mitochondrial swelling and destruction) previously seen in our laboratory. The cellular events described here suggest that cytoplasmic, as well as nuclear, changes (occurring within the same time intervals) may both be relevant to the antitumor effects of cisplatinum.