which is extremely active in human serum it is preferred according to the invention to administer tetrahydrouridine h 4 u a potent inhibitor of this enzyme either concurrently with or at about the same time as administration of the deoxycytidine compound our previous enzyme kinetic studies with 5 bromo 2 39 deoxycytidine brdc and 5 iodo 2 39 deoxycytidine idc indicate that they would not be suitable in this approach to circumvent catabolism because they are poor substrates for deoxycytidine kinase unlike brdc chlorodeoxycytidine cldc does not require deamination at the nucleoside level for its anabolism because it possesses a reasonable km value 56 u03bcm with respect to mammalian deoxycytidine kinase compared to 400 u03bc m for brdc and 2 u03bcm for dc studies with hep 2 cells suggest that cldc h 4 u is metabolized as follows str1 1 deoxycytidine kinase 2 deoxycytidylate deaminase dcmpd 3 thymidylate kinase 4 dna polymerase these four enzymes are elevated in many human tumors for example dcmpd activity in human malignant tumors is 20 80 fold higher than that of normal tissue in x radiation studies with hep 2 cells we have obtained 3 4 3 7 fold dose increase effects cells were preincubated with inhibitors of de novo pyrimidine synthesis n phosphonacetyl l aspartate pala and 5 fluorodeoxyuridine fdu for 20 hours and 5 hours respectively and.