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Effect of 3-Aminobenzamide on the Rate of Ligation during Repair of Alkylated DNA in Human Fibroblasts¹

Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, California 94143

3-Aminobenzamide, an inhibitor of polyadenosine diphosphoribose polymerase, produced rapid reversible changes in singlestrand break frequencies in DNA from primary human fibroblasts damaged by alkylating agents, but it did not cause such changes in the DNA of cells damaged by ultraviolet light. The increase in single-strand peak frequencies was not due to an accumulation of blocked repair sites, such as occurs with DNA polymerase inhibitors, but to a delay in the rejoining of induced breaks. 3-Aminobenzamide increases the net break frequency that results from a dynamic balance between excision and ligation. This balance appears to be regulated at the ligation step by adenosine diphosphate ribosylation, which is rapidly altered by addition or removal of 3-aminobenzamide. The rapidity with which strand break frequencies change in the presence of 3-aminobenzamide implies that individual strand breaks resulting from excision at any time after exposure have a lifetime of no more than about 30 min in the cell.

¹ This work was supported by the United States Department of Energy. Part of this work was presented at the Princess Takamatsu Cancer Research Fund Symposium, "ADP-Ribosylation, DNA Repair, and Cancer," in Tokyo, Japan, November 1982 (9).

² To whom requests for reprints should be addressed.

Received 12/ 2/82. Accepted 3/23/83.

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