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Effects of the cytostatic drug cis-platinum on the developing neocortex of the mouse.

The effects of the new cytostatic drug cis-diamminedichloroplatinum(II) (cis-platinum) on the developing neocortex of NMRI mouse embryos or fetuses were investigated using light- and electron-microscopic methods. Single doses of 20 mg cis-platinum/kg were applied intraperitoneally on day 10, 11, . . ., or 16 of gestation. After treatment on day 10 or 11-i.e., during the phase of organogenesis-no morphological alterations could be detected in the neuroepithelium. However, after treatment on day 12 or later, the mitotic activity was markedly reduced and a great number of cells had become necrotic within 12-24 h after application of the drug. At the ultrastructural level, the development of necroses began with a condensation of the chromatin, culminating in the formation of large condensation plaques and shrinkage and fragmentation of the cytoplasm. The observed necroses can be classified according to Schweichel and Merker as type I necroses. It is argued that the apparent teratogenic inefficiency of cis-platinum on days 10 and 11 of murine pregnancy is caused by the inability of cis-platinum to pass the placental barrier at this stage of pregnancy.