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Mechanisms of induction of SCE and mutations by BrdU and CldU and the use of inhibitors of DNA repair to study mechanisms of radiation-induced chromosome aberrations

Thesis/Dissertation ·
OSTI ID:5748472
The induction of sister chromatid exchanges (SCE) and specific locus mutations was studied by utilizing incorporation into DNA of the nucleoside analogues 5-bromo-and 5-chlorodeoxyuridine (BrdU and CldU). CldU was found to induce SCE seven-times more efficiently than BrdU at equal extracellular concentrations. This induction was linearly associated with substitution for thymidine from 0.5-20 ..mu..M. In these experiments, specific locus mutations were not detected at concentrations less than 50 ..mu..M and were not correlated with SCE induction. At concentrations greater than 50 ..mu..M, the mutagenicity of CldU and BrdU was similar, although BrdU was slightly more mutagenic than CldU. In the examination of radiation-induced chromosome aberrations in mammalian lymphocytes, 3-aminobenzamide and cytosine arabinoside, which are excision repair inhibitors, were used to show that the induction of chromosome aberrations depends upon the ratio of base damage to directly-induced DNA strand breaks for a particular radiation quality. In addition, it was shown that sensitivity of various mammalian species to X ray-induced aberrations depends upon the rate of repair of base damage.
Research Organization:
Tennessee Univ., Knoxville (USA)
OSTI ID:
5748472
Country of Publication:
United States
Language:
English