Synchronized suspension cultures of Chinese hamster ovary (CHO) cells were labeled with ('125)I-iododeoxyuridine (('125)IUdR) in the presence and absence of drugs to permit the selective incorporation of ('125)IUdR into different subfractions of DNA. Control experiments with cells subjected to random labeling with ('125)IUdR yielded a dose-survival curve with a D(,o) of 96 decays/cell. To evaluate the possibility that damage to mitochondrial DNA might contribute to the lethal effects of radiation, the ('125)I response was examined for cells labeled in the presence of berenil, a drug which selectivity inhibits mitochondrial DNA replication. Inhibition of ('125)I incorporation into mitochondrial DNA did not change the overall radiation response of CHO cells. It can be concluded, therefore, that damage to mitochondrial DNA does not contribute to radiation-induced cell lethality, and the primary target for radiation death must be located in the cell nucleus. / To test the hypothesis that the nuclear genome represents a homogeneous target for radiation damage, the ('125)I response of randomly labeled cells was compared to that of cells where only a minute subfraction of the nuclear DNA was labeled. Non-random labeling of a subfraction of DNA was achieved by pairing ('125)IUdR with aphidicolin, a drug which appears to restrict DNA replication to the small portion of the DNA which is closely associated with the replication complex at the nuclear matrix. ('125)I decays in this subfraction of DNA proved to be considerably more toxic (D(,0): 30 decays/cell) to CHO cells then randomly distributed ('125)I decays (D(,0): 96 decays/cell). / These findings suggest that the cellular genome is not a uniform target for radiation damage. The presence or absence of mitochondrial DNA damage does not influence the extent of radiation-induced cell death. Even within the nuclear genome, ('125)I decays in different subfractions of DNA result in radically different biological effects. It must be concluded, therefore, that the cellular genome is subdivided into target loci which are inhomogeneous with respect to radiation sensitivity. / Source: Dissertation Abstracts International, Volume: 45-06, Section: B, page: 1696. / Thesis (Ph.D.)--The Florida State University, 1984.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_75348 |
| Contributors | YASUI, LINDA S., Florida State University |
| Source Sets | Florida State University |
| Detected Language | English |
| Type | Text |
| Format | 96 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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