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Identification of 7-Carboxymethylguanine in DNA from Pancreatic Acinar Cells Exposed to Azaserine¹

Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03755

Studies were undertaken to determine the identity of an azaserine:DNA adduct. The most probable adduct, 7-carboxymethylguanine, was synthesized. DNA isolated from pancreatic acinar cells treated in culture with [¹⁴C]azaserine was hydrolyzed under neutral conditions to liberate N-alkylated purines. The neutral hydrolysate was subjected to high-performance liquid chromatography along with the synthetic standard. One of the radioactive peaks from the treated DNA was found to cochromatograph with 7-carboxymethylguanine in three systems: reverse phase; anion exchange; and ion pair reverse phase. These results suggest that azaserine metabolism in acinar cells results in carboxymethylation of DNA, supporting previously proposed models of azaserine degradation.

¹ This work was supported by NIH Grant CA 17843.

² Recipient of NIH Fellowship F32-CA06855. Present address: Department of Environmental Medicine, New York University Medical Center, 550 First Avenue, New York, N. Y. 10016.

³ To whom requests for reprints should be addressed.

Received 9/16/81. Accepted 1/ 4/82.

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