Mutational specificity of oxidative DNA damage

Retèl, J.; Hoebee, Barbara; Braun, Jacqueline E.F.; Lutgerink, Jan T.; Akker, Eric van den; Wanamarta, A.Handayani; Joenje, Hans; Lafleur, M.V.M.

doi:10.1016/0165-1218(93)90094-t

Cited by 76 publications

(42 citation statements)

References 83 publications

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“…Indeed, there is some evidence suggesting that the DNA damage repair machinery may be mechanistically involved in the ALT pathway (Henson et al, 2002). In this context it should be emphasized that telomeres, on account of their guanine-rich composition, are several fold more susceptible to oxidative stress-mediated damage than non-telomeric DNA (Retel et al, 1993;Henle et al, 1999) and thus represent a prime site for recombinatorial events. The pattern of increased TRF heterogeneity within the same cell (Fig.…”

Section: Discussionmentioning

confidence: 99%

Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells

Kurz

Decary

Hong

et al. 2004

Journal of Cell Science

430

278

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Replicative senescence and oxidative stress have been implicated in ageing, endothelial dysfunction and atherosclerosis. Replicative senescence is determined primarily by telomere integrity. In endothelial cells the glutathione redox-cycle plays a predominant role in the detoxification of peroxides. The aim of this study was to elucidate the role of the glutathione-dependent antioxidant system on the replicative capacity and telomere dynamics of cultured endothelial cells. Human umbilical vein endothelial cells were serially passaged while exposed to regular treatment with 0.1 μM tert-butyl hydroperoxide, a substrate of glutathione peroxidase, or 10 μM L-buthionine-[S,R]-sulphoximine, an inhibitor of glutathione synthesis. Both treatments induced intracellular oxidative stress but had no cytotoxic or cytostatic effects. Nonetheless, treated cultures entered senescence prematurely (30 versus 46 population doublings), as determined by senescence-associated β-galactosidase staining and a sharp decrease in cell density at confluence. In cultures subjected to oxidative stress terminal restriction fragment (TRF) analysis demonstrated faster telomere shortening (110 versus 55 bp/population doubling) and the appearance of distinct, long TRFs after more than 15-20 population doublings. Fluorescence in situ hybridisation analysis of metaphase spreads confirmed the presence of increased telomere length heterogeneity, and ruled out telomeric end-to-end fusions as the source of the long TRFs. The latter was also confirmed by Bal31 digestion of genomic DNA. Similarly, upregulation of telomerase could not account for the appearance of long TRFs, as oxidative stress induced a rapid and sustained decrease in this activity. These findings demonstrate a key role for glutathione-dependent redox homeostasis in the preservation of telomere function in endothelial cells and suggest that loss of telomere integrity is a major trigger for the onset of premature senescence under mild chronic oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells

Kurz

Decary

Hong

et al. 2004

Journal of Cell Science

430

278

View full text Add to dashboard Cite

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“…OH radicals and O2 are considered the most important biologically relevant oxygen species; however they are able to react directly with all kind of cells components including cellular DNA. The oxidative DNA damage introduced by direct reaction of these radicals, leads to aberration on base pairs (Retel et al, 1993). In other studies, Goodale et al, (2008), showed that aquatic chromium is both increased cytotoxic and genotoxic to fish cells.…”

Section: Chromosomal Aberration Test (Cat)mentioning

confidence: 99%

Scenario of Genotoxicity in Fishes and Its Impact on Fish Industry

Mir¹,

Khan²,

Bhat³

et al. 2014

IOSRJESTFT

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“…The most frequent modification of DNA linked to ROS is the formation of 8-OH-dG, resulting from attack of either a hydroxyl radical or singlet oxygen on deoxyguanosine. 8-OH-dG has a highly mutagenic potential, as 5-hydroxymethyl-2-deoxyuridine (Retel et al, 1993). With relative frequency, the cell will evade DNA damage using specific DNA polymerases and enter DNA replication creating mutations and chromosomal lesions.…”

Section: Ros and Carcinogenesismentioning

confidence: 99%