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Molecular Radiobiology of Human Cell Lines

III. Radiation-sensitizing Properties of 5-Iododeoxyuridine^*

( McArdle Memorial Laboratory, University of Wisconsin, Madison, Wisconsin)

The radiosensitizing effects of 5-iododeoxyuridine (IUdR) incorporation into the DNA of human cells were systematically evaluated. The mode and degree of IUdR labeling were determined by analytical equilibrium-density-gradient ultracentrifugation. X-ray sensitization was found to depend on the total degree of thymidine replacement by IUdR and not on its distribution between the DNA strands. The factor of x-ray sensitization varied from 1.2 to 3.2 for cells grown at 10^-7 to 5 x 10^-5 M IUdR, respectively. Still higher x-ray sensitization (3.7 x at 2 x 10^-5 M IUdR) was obtained under conditions of thymidylic acid synthesis inhibition (in the presence of 10^-7 M 5-fluorodeoxyuridine), although cell viability was affected by IUdR in concentrations above 10^-5 M. Equilibrium-density-gradient patterns revealed that the mode of DNA replication in D98/AG cells is of the semi-conservative type and that DNA can under-go more than one round of duplication even at the highest levels of IUdR labeling.

^* Supported by research grant CY-5215 from the National Cancer Institute, U.S.P.H.S.

Received 7/11/62.

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