Mechanisms responsible for the low incorporation into DNA of the thymidine analogue, 5-IODO-2′-deoxyuridine

The comparison of the specific radioactivities of DNA in various tissues of the rat, 1 or 2 hr after injection of either [2-¹⁴C] thymidine or [2-¹⁴C] iododeoxyuridine confirms that IdU is less readily incorporated into DNA than dT and that the ratio between the uptake of IdU and dT varies from tissue to tissue. By incubating identical amounts of either [2-¹⁴C]-IdU or [2-¹⁴C]-dT with extracts of the same tissues, a great difference exists between the phosphorylation of the two substrates, phoshorylation of IdU being almost stopped at the monophosphate level, whereas that of dT proceeds to the triphosphate. The low level of IdUTP formation by the system might account for the poor incorporation of IdU into DNA The comparison of the results obtained with normal and regenerating liver supports the hypothesis that phosphorylation of dT and IdU are catalyzed by the same sequence of enzymes.