CHO cells were pulse-labeled with $\rm\sp{125}I$-iododeoxyuridine during early-S phase, harvested 30 min or 5 h after labeling for accumulation of $\rm\sp{125}I$ decays. Cells harvested 30 min after labeling yielded low-LET survival curves (large shoulder, $\rm D\sb0$ 136 decays/cell); cells harvested at hour 5 showed a high-LET pattern of cell killing (no shoulder, $\rm D\sb0$ 45 decays/cell). Surprisingly, the low-LET to high-LET shift in $\rm\sp{125}I$ action was abolished in cells previously exposed to HAT medium; both 30 min and 5 h groups exhibited high-LET-type cell killing (no shoulder, $\rm D\sb0$ 52 decays/cell). The striking difference in cell death was not accompanied by any change in the induction or repair of DNA DSBs as measured by neutral filter elution. These findings suggest that cell killing may not be directly linked to DNA DSBs, and support our earlier conclusion that damage to higher-order genome structures may be important in radiation-induced cell death. / In related experiments, synchronized CHO cells were pulse-labeled with $\rm\sp{125}IUdR$ in S phase and harvested for decay accumulation at the $\rm G\sb2$ phases of two successive cell cycles. When decays were accumulated during the first $\rm G\sb2$ phase after labeling, cell survival followed a high-LET-type pattern characteristic of single-hit kinetics of cell killing (N = 1, $\rm D\sb0$ 40 decays/cell). In contrast, decays during the second $\rm G\sb2$ phase induced cell death with dual-hit kinetics (N = 2, $\rm D\sb0$ 80 decays/cell). A similar divergence in $\rm\sp{125}I$ action was also observed for micronucleus formation and HGPRT mutations. In short, $\rm\sp{125}I$-induced cellular damage can vary depending on whether the decays occur in daughter (first $\rm G\sb2)$ or parental (second $\rm G\sb2)$ DNA. These results imply that parental and daughter DNA strands show different spatial organization in the mammalian genome. / Source: Dissertation Abstracts International, Volume: 56-07, Section: B, page: 3633. / Major Professor: Kurt G. Holer. / Thesis (Ph.D.)--The Florida State University, 1995.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_77506 |
| Contributors | Lin, Xiao., Florida State University |
| Source Sets | Florida State University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | 84 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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