Effects of inhibitors on repair of DNA in normal human and xeroderma pigmentosum cells after exposure to X-rays and ultraviolet irradiation

Kleijer, Wim J.; Hoeksema, Jetty L.; Sluyter, M.L.; Bootsma, D.

doi:10.1016/0027-5107(73)90010-9

Cited by 38 publications

(9 citation statements)

References 26 publications

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“…However, other drugs, that also bind to DNA, have to be applied in comparably high concentrations to inhibit SSB repair . Kleijer et al (1973) found a decrease in SSB repair at 20 µg/ml Actinomycin D but no effect at 2µg/ml, in agreement with Sawada and Okada (1970) and Elkind and Chin-Mei Chang-Liu (1972) .…”

Section: Discussionsupporting

confidence: 87%

“…Interaction of drugs with repair of radiation damage has also been investigated (Cleaver 1969, Sawada and Okada 1970, Kleijer, Hoeksema, Sluyter and Bootsma 1973, Klein, Kocsis and Altmann 1975 . Inhibition of repair was found using substances which affect the energy metabolism of cells (Moss, Dalrymple, Sanders, Wilkinson andNash 1971, Kann, Kohn andLyles 1974) .…”

Section: Introductionmentioning

confidence: 98%

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Effects of Daunomycin and Radiation on Cell-survival and Repair of DNA Single-strand Breaks

Baisch

Linden

Weigert

1977

International Journal of Radiation Biology and Related Studies

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The combined action of Daunomycin and irradiation was investigated using mouse L-929 cells in culture. Survival of cells was measured with the colony assay. Sedimentation in alkaline sucrose gradients was used to study repair of DNA single-strand breaks (SSB) in the presence of various concentrations of Daunomycin. A small increase in radio-sensitivity, as measured by decreasing Do, was obtained for doses of Daunomycin that are considerably toxic to the cells (0.1 microgram/ml). However, the Dq values remained constant even at high concentrations indicating that Daunomycin does not interfere with recovery processes. The rate of rejoining of SSB remained constant up to 1.0 microgram/ml, whereas concentrations of Daunomycin as high as 10 microgram/ml reduced the velocity of repair by a factor of 13. Our data show that concentrations of Daunomycin similar to those required for other DNA-binding drugs are required to inhibit SSB repair. For clinical purposes, no increase in tumour-killing efficiency may be expected from a combined treatment with Daunomycin and radiation.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 98%

Effects of Daunomycin and Radiation on Cell-survival and Repair of DNA Single-strand Breaks

Baisch

Linden

Weigert

1977

International Journal of Radiation Biology and Related Studies

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“…Cells cultured from persons with the disease xeroderma pigmentosum (XP) are apparently defective in an early step of the excision repair process following UV irradiation, probably the incision step (1)(2)(3)(4). However, such cells have been divided into at least five complementation groups by cell fusion (5), and the study in extracts of XP cell lines of enzyme activities believed to be involved in UV excision repair (6)(7)(8)(9)(10) has not adequately explained the general incision defect.…”

mentioning

confidence: 99%

A cell-free assay measuring repair DNA synthesis in human fibroblasts.

Ciarrocchi¹,

Linn²

1978

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

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Osmotic disruption of confluent cultured human fibroblasts that have been irradiated or exposed to chemical carcinogens allows the specific measurement of repair DNA synthesis using dTTP as a precursor. Fibroblasts similarly prepared from various xeroderma pigmentosum cell lines show the deficiencies of UV-induced DNA synthesis predicted from in vivo studies, while giving normal responses to methyl methanesulfonate. A pyrimidine-dimer-specific enzyme, T4 endonuclease V, stimulated the rate of UV-induced repair synthesis with normal and xeroderma pigmentosum cell lines. This system should prove useful for identifying agents that induce DNA repair, and cells that respond abnormally to such induction. It should also be applicable to an in vitro complementation assay with repair-defective cells and proteins obtained from repairproficient cells. Finally, by using actively growing fibroblasts and thymidine in the system, DNA replication can be measured and studied in vitro.Cells cultured from persons with the disease xeroderma pigmentosum (XP) are apparently defective in an early step of the excision repair process following UV irradiation, probably the incision step (1-4). However, such cells have been divided into at least five complementation groups by cell fusion (5), and the study in extracts of XP cell lines of enzyme activities believed to be involved in UV excision repair (6-10) has not adequately explained the general incision defect. As an alternative means to study this phenomenon, we have developed a cell-free system for observing repair DNA synthesis that both demonstrates the XP defect and is permeable to exogenous repair proteins. The system should provide a means of identifying and assaying for the protein(s) defective in the XP cells. In addition, by exhibiting repair DNA synthesis in reponse to carcinogens and x-rays, it should be useful for identifying both agents that induce DNA repair and cells that respond abnormally to such induction.MATERIALS AND METHODS Growth, Treatment, and Osmotic Disruption of Cells. Fibroblast lines were obtained from the American Type Culture Collection (ATCC) and from the Naval Biomedial Research Laboratory (Oakland, CA) and grown in Dulbecco's modified Eagle's medium containing 10% fetal calf serum and 1% antibiotic-antimycotic solutions in a humidified 5% CO2 incubator at 37°. Transfer to 6-cm plastic petri dishes was at a density of 2.5 X 105 cells per plate. All manipulation was done in dim yellow light, avoiding exposure to white light. Mycoplasma contamination was tested according to Schneider et al. (11); no contamination was found.A 6-cm plate of fibroblasts (7-20 days old) containing roughly 106 cells was washed with phosphate-buffered saline (137 mM NaCI/2.7 mM KCI/6.46 mM Na2HPO4/1.47 mM KH2PO4), the liquid was drained off, and the cells were irradiated or treated with carcinogens. One milliliter of 0.05% trypsin was added, the plates were incubated for 5 min at 370, and the cells were then transferred to a plastic tube and chilled. The plates were wa...

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“…IA induced low numbers of SCE in V79 cells (Connell and Duncan 1981) and also chromosomal aberrations in CHO cells which was reported to be due to secondary effects occurring due to its cytotoxicity (Hilliard et al 1998). However, Kleijer et al (1973) have reported that IA induced a small number of breaks in the DNA of T cells and also inhibited rejoining of single strand breaks induced by X-rays by inhibiting enzymes directly. A few papers have explained the role of IA in the regulatory mechanism of carbohydrate metabolism (Wu and Racker 1958) and also the mechanism by which halogenacetates interact with -SH compounds (Dickens 1933).…”

Section: Discussionmentioning

confidence: 99%

Modification of Gamma Radiation and 4-Nitroquinoline 1-Oxide Induced Genotoxicity by Tumour Promoter Iodoacetate

Anjaria

Bhat

Shirsath

et al. 2008

International Journal of Human Genetics

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Modifying effects of tumour promoter Iodoacetic Acid -sodium salt (IA) was studied on 60 Co gamma radiation and 4-Nitroquinoline 1-oxide (4-NQO) induced recombination (gene conversion), back mutation and aberrant colony formation (ACF) using eukaryotic model system, yeast. Cells were exposed to 0-400 Gy of radiation or were treated with 0.15-1.5 mM 4-NQO and grown on the media containing 0-200 µg IA/ml. The results indicated that IA reduced the frequencies of spontaneous; gamma radiation as well as 4-NQO induced back mutation and ACF significantly. Further, it had no effect on spontaneous, radiation or 4-NQO induced recombination (gene conversion) frequency. These observations suggest that IA does not act like other tumour promoters, which enhance the frequency of genetic events induced by carcinogens in vitro.

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Effects of inhibitors on repair of DNA in normal human and xeroderma pigmentosum cells after exposure to X-rays and ultraviolet irradiation

Cited by 38 publications

References 26 publications

Effects of Daunomycin and Radiation on Cell-survival and Repair of DNA Single-strand Breaks

Effects of Daunomycin and Radiation on Cell-survival and Repair of DNA Single-strand Breaks

A cell-free assay measuring repair DNA synthesis in human fibroblasts.

Modification of Gamma Radiation and 4-Nitroquinoline 1-Oxide Induced Genotoxicity by Tumour Promoter Iodoacetate

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