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DNA Replication in X-Irradiated Human Lymphocytes¹

The Joseph Gottstein Memorial Laboratory, Department of Pathology, School of Medicine, University of Washington, Seattle, Washington 98195, and The Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Human peripheral blood lymphocytes are well-differentiated cells. Ordinarily, they do not divide and are considered to be in the G_o stage of the cell cycle. These cells can be stimulated to undergo DNA replication in culture by mitogens such as phytohemagglutinin. In the present study, we have examined cellular and biochemical events that occur after exposure of lymphocytes to X-irradiation. Irradiation with up to 100 rads, prior to stimulation with phytohemagglutinin, did not interfere with DNA replication. At later periods, DNA replication was inhibited proportionally to the amount of radiation. In comparison to DNA synthesis, the effect of X-irradiation on RNA and protein synthesis in phytohemagglutinin-stimulated lymphocytes was less marked. Furthermore, X-rays did not inhibit either the induction or the continual synthesis of DNA polymerase- or -ß in response to phytohemagglutinin. Kinetic studies with different nucleotide substrates suggest that cellular pools of nucleotides are not significantly altered by X-irradiation. Thus, the inhibition of DNA synthesis in irradiated cells is likely to be due to damage to the cellular DNA template. The inhibition of DNA synthesis was accompanied by accumulation of cells in the G₂ and M stages of the cell cycle, suggesting that inhibition of DNA replication by X-irradiation is a postmitotic event.

¹ This work was supported by Grants CA-06551, RR-05539, CA-11524, CA-12818, CA-15139, and CA-06927, awarded by the National Cancer Institute, Department of Health, Education, and Welfare, and by an appropriation from the Commonwealth of Pennsylvania. Cytofluorometric studies were done at the cytokinetics laboratory of Sidney Farber Cancer Center which was supported by National Cancer Institute Grant GA-20008.

² Present address: Department of Medicine, King George's Medical College, Lucknow, India.

³ Present address: Comprehensive Cancer Center for State of Florida, University of Miami Medical School, P. O. Box 520875, Biscayne Annex, Miami, Fla. 33152.

⁴ To whom reprint requests should be addressed, at The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology SM-30, University of Washington School of Medicine, Seattle, Wash. 98195.

Received 3/10/80. Accepted 7/10/81.