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Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
Deoxyribonucleoside incorporation and the role of hydroxyurea were investigated in alkylated, nondividing human lymphocytes. Both thymidine and deoxycytidine incorporation in the presence of hydroxyurea increased after damage with nitrogen mustard or methyl methanesulfonate. Neither deoxyadenosine nor deoxyguanosine incorporation was stimulated by these agents. Data obtained after actinomycin D and KOH digestion suggested that most of the deoxyadenosine and deoxyguanosine were utilized for RNA synthesis, presumably via the salvage pathway. Arabinofuranosylcytosine, which probably acts by chain termination of inhibition of DNA polymerase, prevented the stimulation of thymidine incorporation. Cycloheximide, which like hydroxyurea is an indirect inhibitor of DNA synthesis, may be used to demonstrate increased thymidine incorporation after alkylation; however, in its presence, no increase in deoxyadenosine incorporation after alkylation could be detected. The similarity between the results obtained with hydroxyurea and cycloheximide, when considered with our previous studies, suggests that their role is to limit DNA synthesis by indirect means in the occasional dividing cells present.
1 This is Paper 2 of the series, "Studies on DNA Repair in Carcinogenesis." Work was supported by grants from the Health Research and Services Foundation, Pittsburgh, Pa. (M-68), the American Cancer Society (E-129M and IN-58H), and NIH (CA-06074 from the National Cancer Institute and AI-07125 from the National Institute of Allergy and Infectious Diseases).
2 Sarah Mellon Scaife Fellow in Pathology.
3 Present address: Fels Research Institute, Temple University School of Medicine, Philadelphia, Pa. 19140.
4 Present address: Department of Pathology, University of California School of Medicine, La Jolla, Calif. 92037.
Received 2/26/71. Accepted 5/12/71.
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