DNA-repair mechanisms : symposium, Schloss Reinhartshausen/Rhein, Oct. 4th/5th, 1971 / chairman H. Altmann.

Date:
[1972]
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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: DNA-repair mechanisms : symposium, Schloss Reinhartshausen/Rhein, Oct. 4th/5th, 1971 / chairman H. Altmann. Source: Wellcome Collection.

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    breaks share the same rate limiting step. However, three different enzymatic steps appear to limit the rates of UDS induced by ionizing radiations, UDS induced by ultraviolet light, and normal DNA synthesis. Chromosome aberrations induced by physical, chemical and biological agents in human lymphocytes have been the subject of intense study during the past two decades. If we adopt the simple model that the chromosome is basically a double-stranded DNA molecule or a linear array of such molecules, we expect a close relationship between the breakage and repair of DNA and the production of chromosome aberrations. However, no simple relationship exists (7). For example, on the simple model a double-strand break in DNA should result in a terminal deletion in the chromosome. The number of double- Fig. 3. The effect of varying the time between two 450 rad doses on unscheduled DNA synthesis. The lymphocytes were incubated for a total of 2 hrs in 3 HTdR. The effect of a single dose of 450 rad is also shown. strand breaks in lymphocytes is proportional to the dose of ionizing radiation, and the yield is about one double-strand break per cell per rad. The yield of terminal chromosome deletions is also roughly proportional to dose, and the yield is of the order of 10~ 3 deletions per cell per rad. There is a discrepancy of three orders of magnitude, therefore, between the yield of aberrations and yield of double-strand breaks instead of the one to one correspondence ex pected on the simple model. Moreover, there is no evidence for a repair of double-strand DNA breaks that would account for such a discrepancy. Again, on a simple model, chromosome exchange aberrations should result from the interaction of single-strand breaks. However, single-strand breaks show a half- life of about 14 minutes at low X-ray doses, whereas split-dose experiments on the yield of dicentrics suggest a half-life of about an hour. The interaction of radiation-induced breaks is not evident in the experiments on UDS. Fig. 3 shows the results of varying the time between doses. As can be seen, the effect of two 450 rad doses is just equal to that of one 900 rad dose regard