Inhibition ATP of the Growth-inhibitory Effect of Synkavit (2-methyl-1,4-naphthaquinol Bis Disodium Phosphate) on Mouse Ascites Tumour Cells

Ehrlich ascites cells or another strain derived from a spontaneous mouse mammary carcinoma (DiVita's ascites cells) were incubated in vitro at 37° C. at cell concentrations of 1-2 × 10(7) cells/ml. with 10(-4)M Synkavit in Spinner-medium under various conditions. The cells were then inoculated under standard conditions into mice, and the growth of ascites tumour was determined. On this basis, Synkavit has been shown to retard the growth of ascites tumour provided that the cells were incubated in vitro at pH 7.4 for 30 minutes. This retardation of tumour growth was not dependent on the presence of glucose in the incubation medium and could be observed in the presence of about 5% ascitic fluid. However, the retardation appeared to be considerably less marked (though readily detectable) when the incubation with Synkavit was performed anaerobically. The retardation of tumour growth by Synkavit was abolished completely by simultaneous incubation with excess ATP or partially by equimolar ATP. Simultaneous incubation with excess ADP also abolished the retardation by Synkavit of the growth of tumour. Moreover, ATP addition to the medium at a later period appeared to be partially successful in abolishing the Synkavit effect on tumour growth. The mechanism by which ATP reduced the growth-inhibitory effect of Synkavit has been partially clarified by investigating the effect of ATP on the incorporation of a tritiated derivative of Synkavit, TRK 219. The results show that in Ehrlich ascites cells, simultaneous incubation in Spinner-medium with excess, or equimolar, ATP reduced the incorporation of labelled metabolites of Synkavit by 78% or 14% respectively. On the other hand, in a continuous cell line of human epithelial cells (HEp/2), excess ATP reduced the incorporation of metabolites of labelled Synkavit very slightly. These results have been discussed in the light of other evidence to consider the mechanism whereby ATP reduced the growth-inhibitory effects of Synkavit.