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Detection of DNA Single-Strand Breaks Produced during the Repair of Damage by DNA-Protein Cross-Linking Agents

Laboratory of Experimental Pathology, Human Tissue Studies Section, Division of Cancer Cause and Prevention, National Cancer Institute, Bethesda, Maryland 20205

In this investigation, the combination of 1-ß-D-arabinofu-ranosylcytosine and hydroxyurea was used to inhibit the polymerase step of DNA excision repair. The DNA single-strand breaks (SSB), which accumulated in the presence of these agents, were measured by alkaline elution. With this approach, DNA SSB were detected in normal human fibroblasts after exposure to trans-platinum(II)diamminedichloride, formaldehyde, or potassium chromate. These agents all share the common feature that they induce DNA-protein cross-links in mammalian cells. In the case of trans-platinum(II)diammine-dichloride or formaldehyde, the frequency of these SSB was markedly less in excision-deficient xeroderma pigmentosum cells. With chromate, a high level of SSB was induced in both normal and xeroderma pigmentosum cells; these results indicate that chromate damage to DNA is repaired by a mechanism different than the classical excision pathway since xeroderma pigmentosum cells responded normally. Several other agents were investigated with this approach, and no SSB were detected with nickel sulfate, 12-O-tetradecanoylphorbol-13-acetate or abestos fibers in the presence or absence of the polymerase inhibitor. This approach was found to be a very sensitive method to detect DNA excision repair.

¹ Present address: Laboratory of Pathology, National Cancer Institute, NIH.

Received 6/ 8/81. Accepted 9/16/81.

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