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Induction of the DNA Repair Enzyme Uracil-DNA Glycosylase in Stimulated Human Lymphocytes¹

Fels Research Institute and the Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

The capacity of human cells to modulate the synthesis of DNA repair enzymes has been investigated by measuring the induction of the uracil-DNA glycosylase during lymphocyte stimulation. Treatment of peripheral lymphocytes with phytohemagglutinin increased glycosylase activity 10-fold. Glycosylase stimulation was coordinate with the activation of DNA synthesis and DNA polymerase activity. Two chromatographically distinct species of the glycosylase have been resolved; only one species is induced during phytohemagglutinin stimulation. The effect of actinomycin D and cycloheximide on glycosylase induction was determined. Treatment with either inhibitor at 96 hr after phytohemagglutinin addition (maximal induction) decreased glycosylase activity after an appreciable lag period. This suggested that induction of the uracil-DNA glycosylase requires transcription and translation although the enzyme may be quite stable once induced.

¹ This study was supported by NIH Grant ES-01735 and CA-12227.

Received 12/21/78. Accepted 3/13/79.