Cumulative Cytostatic Effect of ICRF 159

Abstract

THE antimitotic action of (±)-1,2-bis (3,5-dioxopiperazin-1-yl) propane (ICRF 159) has been extensively studied in vivo in human¹ and animal tumours^2,3, but its mode of action at the cellular and biochemical level has not yet been elucidated. Although it reduces the rates of DNA, RNA and protein synthesis of cells in vitro⁴, it has also been shown to block the cell generation cycle in the post-DNA synthesis (G₂) phase^5,6. Tumours whose growth is halted contain many large multinucleate cells not seen in control tumours. An attempt has therefore been made to see if the morphological changes produced by the drug in cells grown in vitro could provide an indication of its intracellular site of action and point towards possible mechanisms of action. The cells used were non-synchronised cultures of non-transformed hamster fibroblasts (Nil 8 cells), HeLa cells and fibroblasts derived from a transplantable fibrosarcoma in Syrian hamsters (T17 cells). They were exposed to single daily doses of ICRF 159 for 3 d.