ENHANCEMENT OF MACROPHAGE TUMORICIDAL ACTIVITY BY THE ALKALOID DERIVATIVE UKRAIN - INVITRO AND INVIVO STUDIES

Ukrain is a semisynthetic drug with immunomodulatory properties, deriv ed from Chelidonium majus L. alkaloids and thiophosphoric acid. The ef fect of this compound on the growth of Balb/c syngenic mammary adenoca rcinoma was assessed. Intravenous, but not subcutaneous or intraperito neal, administration of this drug was found to be effective in delayin g tumour growth in an actual therapeutic protocol initiated five days after tumour implantation. No untoward side-effects were observed usin g these in vivo treatment modalities. The role of macrophages in the o bserved retardation of tumour development was investigated using perit oneal exudate macrophages (PEM) in cytotoxicity assays. In previous st udies, the authors have found that PEM of mammary tumour bearing mice lose their capacity to kill a variety of tumour target cells including the in vitro cultured homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5 muM Ukrain for 24 h followed by stimula tion with either IFN-gamma or with LPS + IFN-gamma enhanced their cyto toxic activity. Treatment of PEM from tumour bearing mice with 2.5 muM Ukrain and LPS results in a reversal of their defective cytotoxic res ponse against the DA-3 target cells. Furthermore, Ukrain alone, in the absence of a secondary signal, induced the activation of tumouricidal function of PEM from tumour bearing but not from normal mice. These d ata indicate that Ukrain's in vivo effects against the development of mammary tumours may be due, at least in part, to its ability to restor e macrophage cytolytic function.