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The development of gamma ray damage in chromosomes in relation to cell killing

Thesis/Dissertation ·
OSTI ID:6968680
Virtually every important biological effect of ionizing radiation (IR) relates to the induction of chromosomal aberrations (CA). Study of their development is essential for understanding the biological effects of IR. Potentially lethal damage (PLD) has been defined in terms of changes in survival brought about by the manipulation of conditions to which cells are exposed after IR. One form of PLD is expressed after treatment with anisotonic salt solutions following IR. Changes in cell survival have been attributed to changes in the balance between damage repair and fixation. This study explored the possibility that the decrease in survival found after treatment with hypertonic solutions was caused by an increase in the amount of damage expressed immediately after treatment as interphase chromosome breaks (CB) and therefore, an increase in the amount of PLD available for processing by fixation' and repair.' The premature chromosome condensation technique (PCC) was used to determine that hypertonic treatment given immediately before, during, or immediately after IR did cause an increase in the number of CB measured directly after treatment compared to the same dose given without treatment. Treatment with [beta]-ara-A, a known inhibitor of chromosome rejoining, also showed an increase in CB immediately after hypertonic treatment, indicating that [beta]-ara-A was not simply acting as an inhibition of rejoining. These changes in initial PCC breakage frequency were correlated to increases in CA and decrease in cell survival. Agents, such as IR, known to produce DNA double-strand breaks promptly after treatment have also been shown to produce breaks in interphase chromatin immediately after treatment. Preliminary studies were conducted using restriction endonucleases which produce only DNA double-strand breaks to establish that such DNA breaks can cause CB observed as excess PCC fragments soon after treatment.
Research Organization:
Colorado State Univ., Fort Collins, CO (United States)
OSTI ID:
6968680
Country of Publication:
United States
Language:
English