DNA-REPLICATION IN X-IRRADIATED HUMAN-LYMPHOCYTES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (10) , 3973-3978
Abstract
Human peripheral blood lymphocytes are well-differentiated cells. Ordinarily they do not divide and are considered to be in the G0 stage of the cell cycle. These cells can be stimulated to undergo DNA replication in culture by mitogens such as phytohemagglutinin. Cellular and biochemical events that occur after exposure of lymphocytes to X-irradiation were examined. Irradiation with < 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. X-rays did not inhibit either the induction or the continual synthesis of DNA polymerase-.alpha. or -.beta. in response to phytohemagglutinin. Kinetic studies with different nucleotide substrates suggest that cellular pools of nucleotides are not significantly altered by X-irradiation. 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. [This system offers advantages in screening large populations for abnormal response to radiation reflecting defective DNA repair.].