Role of DNA polymerase α in chromosomal aberration production by ionizing radiation

The authors have shown that aphidicolin, like other inhibitors of DNA synthesis, both induces chromosomal aberrations in human peripheral lymphocytes and, as a post-treatment, interacts synergistically with X rays to produce greatly enhanced aberration yields. Because DNA polymerase α is the only DNA-synthetic or repair enzyme known to be affected by aphidicolin, the authors infer that this enzyme is directly involved in the repair of DNA lesions which, if unrepaired, can result in visible chromosomal aberrations. The present experiments were undertaken to further explore the effects of aphidicolin in human lymphocytes in the post-DNA-synthetic G2 phase of the cell cycle. Earlier experiments in which cells were simply fixed at times after treatment when the frequency of metaphases in the DNA-synthetic S phase of the cell cycle is zero in typical percentage labeled mitoses curves for human lymphocytes did not completely rule out the possibility that the aberrations induced by aphidicolin actually arose in a small subpopulation of cells actually in the S phase, and not in G2 cells. Furthermore, the yield of X-ray-induced aberrations in G2 cells falls rapidly as a function of increasing irradiation-fixation interval, so comparisons of yields at particular fixation times can be misleading if the cells in each group do not progress through G2 at the same rate. The experiments reported here utilized labeling with tritiated thymidine to positively identify cells in the S phase at the time of treatment and serial Colcemid collections and fixations to determine aberration yields over as much of the G2 phase as feasible