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U.S. Department of Energy
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Radiation lethality and the cellular genome

Thesis/Dissertation ·
OSTI ID:5808109
Synchronized suspension cultures of Chinese hamster ovary (CHO) cells were labeled with /sup 125/I-iododeoxyuridine (/sup 125/IUdR) in the presence and absence of drugs to permit the selective incorporation of /sup 125/IUdR into different subfractions of DNA. To evaluate the possibility that damage to mitochondrial DNA might contribute to the lethal effects of radiation, the /sup 125/I response was examined for cells labeled in the presence of berenil, a drug which selectivity inhibits mitochondrial DNA replication. Inhibition of /sup 125/I incorporation into mitochondrial DNA did not change the overall radiation response of CHO cells. To test the hypothesis that the nuclear genome represents a homogenous target for radiation damage, the /sup 125/I response of randomly labeled cells was compared to that of cells where only a minute subfraction of the nuclear DNA was labeled. /sup 125/I decays in this subfraction of DNA proved to be considerably more toxic to CHO cells then randomly distributed /sup 125/I decays. 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, /sup 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 inhomogenous with respect to radiation sensitivity.
Research Organization:
Florida State Univ., Tallahassee (USA)
OSTI ID:
5808109
Country of Publication:
United States
Language:
English