Enhancement and depression by inosine of the growth inhibitory action of 5-fluorouracil on cultured Jensen tumor cells

Continuous exposure of Jensen tumor cells in vitro to 1 mM inosine following a 1 hr exposure to 5-fluorouracil resulted in a 5-fold potentiation of growth inhibition. This effect was abolished by the simultaneous presence of 1 mM cytidine and was attributable to altered metabolic processing of drug anabolites after the uptake of 5-fluorouracil had ceased. In contrast, antagonism to 5-fluorouracil was seen when the cells were exposed successively to 1 mM inosine for 1.5 hr and to 5-fluorouracil for 1 hr. In this case the inhibitory action of the drug was diminished by nearly one-half. Quantitation of the potentiation and antagonism was based upon growth delays measured from growth curves obtained by serial photomicrography.