Chinese hamster ovary cells were synchronized at the G$\sb1$/S boundary of the cell cycle and labeled for 10 min with $\sp{125}$I-iododeoxyuridine. Samples were frozen for decay accumulation between 15-480 min after labelling. Cells frozen within 1 h after labeling yielded a low LET survival response with a pronounced shoulder and a large D$\sb0$ (255 decays/cell). With longer chase periods the shoulder and the D$\sb0$ decreased progressively and cells harvested 5 h after labeling exhibited a high LET survival response (D$\sb0$: 65 decays/cell). If DNA is assumed to be the sole target for radiation-induced death, these results indicate that DNA maturation increases radiation damage to DNA or reduces repair. Alternatively, if radiation death involves damage to higher-order structures in the nucleus, the findings suggest that newly replicated DNA is not attached to these structures during the initial low LET period, but $\sp{125}$I starts to induce high LET effects as labeled DNA becomes associated with the target structure(s). On balance, our data favor the latter interpretation. / In related experiments, exponentially growing cells were labeled with $\sp{125}$I-iododeoxyuridine for 12 h. Mitotic cells were selected, plated for cell cycle traverse, and harvested during successive stages of the cell cycle for decay accumulation. $\sp{125}$I damage during G$\sb1$ resulted in shoulderless exponential survival curves with a D$\sb0$ of 60-65 decays/cell. Resistance to $\sp{125}$I decays increased as cells progressed through S and the survival curves of cells in late S/G$\sb2$ were characterized by a pronounced shoulder and a D$\sb0$ of 127-139 decays/cell. These findings suggest that the primary target for radiation death is duplicated during S with G$\sb1$ cells containing one set and G$\sb2$ cells two sets of targets. Dual targets, although located within a single cell, act independently, as if already distributed between separate daughter cells. Analysis of the data suggests that the emergence of a shoulder and doubling of the D$\sb0$ in late S/G$\sb2$ cells represents an artifact of the colony formation assay which systematically overstates cell survival when intracellular target multiplicity exceeds 1. / Source: Dissertation Abstracts International, Volume: 53-03, Section: B, page: 1235. / Major Professor: Kurt G. Holer. / Thesis (Ph.D.)--The Florida State University, 1992.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_76638 |
| Contributors | van Loon, Nanette Marie., Florida State University |
| Source Sets | Florida State University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | 119 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
Page generated in 0.0019 seconds