This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brown, A. J. Articles by Waters, R. Search for Related Content PubMed PubMed Citation Articles by Brown, A. J. Articles by Waters, R.

Overlapping Pathways for Repair of Damage from Ultraviolet Light and Chemical Carcinogens in Human Fibroblasts¹

The University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences [A. J. B.] and Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 [A. J. B., R. W.]; Laboratory of Radiobiology, University of California, San Francisco, California 94143 [T. H. F., J. E. C.]; and Medische Biologische Laboratorium, TNO, Rijswijk, The Netherlands [P. H. M. L., M. H. W.]

DNA excision repair was measured in cultured human fibroblasts after single or dual treatments with ultraviolet radiation, 4-nitroquinoline 1-oxide, or N-acetoxy-2-acetylaminofluorene. Three approaches were used to monitor repair: unscheduled DNA synthesis, measured by autoradiography; repair replication, measured by the incorporation of a density-labeled DNA precursor into repaired regions; and excision of ultraviolet endonuclease-sensitive sites. When a single repair-saturating dose of one of the three carcinogens was administered, little stimulation of unscheduled DNA synthesis or repair replication could be observed by additional treatment with one of the other carcinogens. In no instance was total additivity of repair observed. These observations were confirmed by showing that the excision of endonuclease-sensitive sites produced by ultraviolet damage (i.e., pyrimidine dimers) was inhibited by exposure to 4-nitroquinoline 1-oxide and N-acetoxy-2-acetylaminofluorene. The data indicate that the repair of lesions induced by these substances may have common rate-limiting steps, a conclusion previously indicated by the repair deficiency in xeroderma pigmentosum cells in which a single mutation eliminates the repair of damage caused by each of these agents.

¹ Supported by the Division of Biomedical and Environmental Research, United States Department of Energy, partly under Contract W-7405-eng-26 with the Union Carbide Corporation, and the Medische Biologische Laboratorium, TNO, Rijswijk, The Netherlands.

² Recipient of Grant GM 1974-09 from the National Institute of General Medical Sciences, NIH.

³ Recipient of NIH Training Grant 5T01GMOD829.

⁴ To whom requests for reprints should be addressed.

Received 5/22/78. Accepted 3/28/79.