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Inhibition of Landschütz Ascites Tumour Growth by Metal Chelates Derived from 3,4,7,8-Tetramethyl-1,10-phenanthroline

British Journal of Cancer
Nature Publishing Group
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  • Biology
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195 INHIBITION OF LANDSCHUTZ ASCITES TUMOUR GROWTH BY METAL CHELATES DERIVED FROM 3,4,7,8-TETRAMETHYL- 1,10-PHENANTHROLINE F. P. DWYER,* E. MAYHEW,t E. M. F. ROE AND A. SHULMAN+ From the Chester Beatty Research Institute, Institute of Cancer Research: Royal Cancer Hospital, Fulham Road, London, S. W.3 Received for publication September 30, 1964 THE ability of metal chelates derived from copper and dimethylglyoxime or platinum, palladium and 6-mercaptopurine to inhibit the growth of tumour cells has been demonstrated by Takamiya (1960) and Kirschner, Yung-Kang Wei and Francis (1962) respectively. Further, Lenta and Riehl (1960) have demonstrated the ability of metal chelates derived from ethylene diamine tetraacetic acid (E.D.T.A.) to influence oxidative processes in liver mitochondria isolated from the mouse hepatoma 98/15. Consequently, it seemed likely that other types of metal chelate would have similar actions, especially those derived from the transition metals, Ru, Os, Ni, Fe, Cu, Co, Zn, Cd, and Mn, and substituted 1,10- phenanthroline or related bases, since these substances have been shown to exert marked effects on a wide variety of biological systems including HeLa cells in culture (White, Harris and Shulman, 1963; Shulman and Dwyer, 1964). The present work reports the effect of the following three metal chelates on the growth of the Landschutz ascites tumour in B alb C+ male or C female mice. (a) bis (3,4,7,8-tetramethyl-1,10-phenanthroline) copper (II) dichloride, called here Cu 1. (b) tris(3,4,7,8-tetramethyl-1,10-phenanthroline)ruthenium (II) dichloride, called here Ru 2. (c) acetylacetonatobis (3,4,7,8-tetramethyl-1, 10-phenathroline) ruthenium (II) chloride, called here Ru 1. The marked stability of cations like Ru 2, both to chemical treatment and under biological conditions, suggests that their biological effects are due to the cation as a whole and not to its constituents, the metal and the ligand (Koch, Rogers, Dwyer and Gyarfas, 1957). While it is likely that

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