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Production of Thymine Glycols in DNA by N-Hydroxy-2-naphthylamine As Detected by a Monoclonal Antibody¹

Biophysics Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan [M. K.] and Department of Biological Sciences, Stanford University, Stanford, California 94305 [S. A. L.]

We have quantitated the production of thymine glycols in DNA following treatment of cultured human fibroblasts or DNA in solution with the carcinogen N-hydroxy-2-naphthylamine. Thymine glycols, detected by using a monoclonal antibody specific to this base damage, were produced in DNA in a dose dependent manner both in vitro and in vivo. Exposure of DNA to N-hydroxy-2-naphthylamine in the presence of catalase and superoxide dismutase, which break down hydrogen peroxide and superoxide anions, respectively, inhibited the production of this base damage. Thymine glycols were efficiently removed from DNA in both normal human fibroblasts and in cells from a patient with xeroderma pigmentosum complementation group A, which are deficient in nucleotide excision repair.

¹ This work was supported by a U.S.-Japan cooperative research program from the National Cancer Institute-JSPS and by USPHS Grant GM09901 to P. C. Hanawalt.

² To whom requests for reprints should be addressed.

³ Present address: Lawrence Berkeley Laboratory, Building 934, University of California, Berkeley, CA 94720.

Received 5/30/85. Revised 9/30/85. Accepted 10/ 2/85.