Variations in Several Responses of HeLa Cells to X-Irradiation during the Division Cycle

Abstract

Several responses of synchronized populations of HeLa S3 cells were measured after irradiation with 220 kev x-rays at selected times during the division cycle. (1) Survival (colony-forming ability) is maximal when cells are irradiated in the early post-mitotic (G(1)) and the pre-mitotic (G(2)) phases of the cycle, and minimal in the mitotic (M) and late G(1) or early DNA synthetic (S) phases. (2) Markedly different growth patterns result from irradiation in different phases: (a) Prolongation of interphase (division delay) is minimal when cells are irradiated early in G(1) and rises progressively through the remainder of the cycle. (b) Cells irradiated while in mitosis are not delayed in that division, but the succeeding division is delayed. (c) Persistence of cells as metabolizing entities does not depend on the phase of the division cycle in which they are irradiated. (3) Characteristic perturbations of the normal DNA synthetic cycle occur: (a) Cells irradiated in M suffer a small delay in the onset of S, a slight prolongation of S, and a slight depression in the rate of DNA synthesis; the major delay occurs in G(2). (b) Cells irradiated in G(1) show no delay in the onset of S, and essentially no alteration in the duration or rate of DNA synthesis; G(2) delay is minimal. (c) Cells irradiated in S suffer an appreciable S prolongation and a decreased rate of DNA synthesis; G(2) delay is shorter than S delay.

Geminin: A good prognostic factor in high‐grade astrocytic brain tumors

“…13 The results of clonogenic survival assays clearly indicate that cells synchronized at the M-phase or at the early S-phase are the most radiosensitive, and cells in G1-phase are comparatively radioresistant. 21,22 From these observations, we propose that the higher the expression of geminin, the higher the proportion of cells in phases other than G1 of the cell cycle, resulting in higher radiosensitivity. Therefore, patients who have high-grade astrocytoma patients with overexpressed geminin have favorable outcomes after surgery and radiation therapy.…”

p16 gene transfer increases cell killing with abnormal nucleation after ionising radiation in glioma cells

“…It is well established that radiation sensitivity varies with the population of the cell-cycle, and that cells at the M-phase and late G1 to the early S phase have great sensitivity (Terasima and Tolmach, 1963;Okada, 1970). Here, we assessed the ability of Ax-hp16 to enhance radiosensitivity in human glioma cell lines that lack p16, but have either wt-p53 or mut-p53.…”

“…The results of clonogenic survival assays clearly indicate that cells synchronised at the late S and early G1 phase are the most radioresistant, whereas cells synchronized at the M phase or at the late G1 to early S phase are the most radiosensitive (Terasima and Tolmach, 1963;Okada, 1970). The regulatory cascade comprising pRb, cyclin D1, CDK4/CDK6 and p16 plays a central role in cell-cycle control, and may govern radiosensitivity as well.…”

Heavy-Ion Radiobiology: Cellular Studies

“…Variations in the radiosensitivity of cultured mammalian cells at different phases of the division cycle have been known since the early 1960s (Tersima and Tolmach, 1961Tolmach, , 1963Sinclair and Morton, 1963. It was not, however, until the late 1960s and early 1970s that the high LET radiations were found to diminish the amplitude of the variation between the most sensitive and the most resistant phases.…”