Rejoining of X-ray Induced Breaks in the DNA of Leukaemia Cells

Lett, J. T.; Caldwell, Ian C.; Dean, C.J.; Alexander, Peter

doi:10.1038/214790a0

Cited by 295 publications

(60 citation statements)

References 11 publications

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“…Several groups have reported that large DNA gets entangled and sediments anomalously (Lett et al, 1967;Ormerod & Lehmann, 1971a;Ormerod & Stevens, 1971). I have shown that the sedimentation profile of bulk DNA is changed when large amounts of DNA are put on the gradient ... , .....…”

Section: Entangling Of Different-sized Strandsmentioning

confidence: 99%

Discontinuous DNA Synthesis in Mammalian Cells

Huberman¹,

Horwitz²

1974

Cold Spring Harbor Symposia on Quantitative Biology

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Section: Entangling Of Different-sized Strandsmentioning

confidence: 99%

Discontinuous DNA Synthesis in Mammalian Cells

Huberman¹,

Horwitz²

1974

Cold Spring Harbor Symposia on Quantitative Biology

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“…Single-strand breaks are the best studied lesions that occur in mammalian DNA after exposure to ionizing radiation (1) and to certain DNA-damaging chemicals (2). Because the repair of these breaks is very rapid and almost complete (3), there has been a tendency to classify single-strand breaks as unimportant lesions in terms of their role in cell killing.…”

mentioning

confidence: 99%

Non-Repairable Strand Breaks Induced by ¹²⁵ I Incorporated into Mammalian DNA

Painter

Young

Bürki

1974

Proc. Natl. Acad. Sci. U.S.A.

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When i2aI is incorporated into Chinese hamster DNA (via 1251-labeled iododeoxyuridine) and the cells are stored at 770K, the resulting decays of the isotope cause 4 to 5 breaks/single-strand per disintegration. On the average, about 50% of these breaks are repaired. In contrast, under the same conditions of storage and in the same range of total strand breaks/cell, 70-100% of the breaks induced by x-radiation are repaired. Thus, the extreme toxicity of 1251 when incorporated into DNA is correlated with the unrepaired breaks caused by decay of this isotope. These results suggest that unrepaired DNA strand breaks may be important in cell killing after treatments which damage DNA.Single-strand breaks are the best studied lesions that occur in mammalian DNA after exposure to ionizing radiation (1) and to certain DNA-damaging chemicals (2). Because the repair of these breaks is very rapid and almost complete (3), there has been a tendency to classify single-strand breaks as unimportant lesions in terms of their role in cell killing. The alkaline sucrose gradient method [originally devised for work with bacteria (4) but quickly adapted for use with mammalian cells], however, is not sensitive enough to detect low percentages of breaks, which, if really left unrepaired, might contribute significantly to the killing of cells.In studies on the action of 1251 incorporated into Chinese hamster V79 DNA (as 125I-labeled iododeoxyuridine), we found that many of the single-strand breaks induced by the decay of this isotope are not repaired. Because 1251 in DNA kills Chinese hamster V79 cells very efficiently (5), we strongly suspect that there is a cause and effect relationship between unrepaired strand breaks induced by 1251 in DNA and cell killing. It is reasonable to believe that this relationship may extend to the action of other agents which cause breakage of cellular DNA. MATERIALS AND METHODSChinese hamster V79 cells were grown in the tissue culture medium described by Burki and Carrano (6)

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“…Major X-ray-induced DNA lesions include singlestrand breaks and base damage-both of which can be repaired in eukaryote cells (for references see Dugle et al 1976). In many different cell types the number of radiation-induced breaks has been shown to decrease significantly during the first 40 min post-irradiation but a later, slower phase of rejoining often follows the initial rapid phase (Lett et al 1967;Donlan and Norman 1971;Horikawa et al 1972;Matsudaira and Furino 1972).…”

Section: Discussionmentioning

confidence: 99%

X-ray Induced Activity of N-Ethylmaleimide-Sensitive DNA Polymerase in Chinese Hamster Cells

Ramsay¹,

Westerman²

1980

Aust. Jnl. Of Bio. Sci.

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Chinese hamster DDN cells have been exposed to low doses of X-irradiation « 15 Gy). These doses have been shown to induce significant levels of repair replication. Levels of activity of DNA polymerase were subsequently measured in cells exposed in G 1 phase of mitosis to 7·5 Gy of X-rays. Following exposure, the activity of this enzyme was observed to rise to a peak within 15 min postirradiation, then decline and then rise again over a long period. The initial rise at least was found to be sensitive to inhibition by N-ethylmaleimide, a known inhibitor of DNA polymerase-o< and DNA polymerase-y at the concentration used. It is therefore suggested that repair of X-ray-induced damage in these DON cells was at least in part dependent upon induced DNA polymerase activity and this may involve DNA polymerase-o< or DNA polymerase-y, or both.

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Rejoining of X-ray Induced Breaks in the DNA of Leukaemia Cells

Cited by 295 publications

References 11 publications

Discontinuous DNA Synthesis in Mammalian Cells

Discontinuous DNA Synthesis in Mammalian Cells

Non-Repairable Strand Breaks Induced by ¹²⁵ I Incorporated into Mammalian DNA

X-ray Induced Activity of N-Ethylmaleimide-Sensitive DNA Polymerase in Chinese Hamster Cells

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Rejoining of X-ray Induced Breaks in the DNA of Leukaemia Cells

Cited by 295 publications

References 11 publications

Discontinuous DNA Synthesis in Mammalian Cells

Discontinuous DNA Synthesis in Mammalian Cells

Non-Repairable Strand Breaks Induced by 125 I Incorporated into Mammalian DNA

X-ray Induced Activity of N-Ethylmaleimide-Sensitive DNA Polymerase in Chinese Hamster Cells

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Non-Repairable Strand Breaks Induced by ¹²⁵ I Incorporated into Mammalian DNA