Free radical-induced double lesions in DNA

Box, Harold C.; Dawidzik, Jean B.; Budzinski, Edwin E.

doi:10.1016/s0891-5849(01)00653-0

Cited by 131 publications

(82 citation statements)

References 71 publications

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“…A higher level of post-thaw DNA strand breaking was effectively detected. Our results also suggest that guanosines are more prone than cytosines to be oxidized during freezing-thawing, as has been reported by other authors (Box et al 2001). On the other hand, not all base oxidizations promote DNA strand breaks, because further digestion with specific endonucleases increased fragmentation rates.…”

Section: Discussionsupporting

confidence: 88%

“…To show the direct effect of oxidization on DNA molecules, we combined the use of EndIII and Fpg digestion with the comet assay showing the presence of oxidized bases in both fresh and cryopreserved samples located in the non-fragmented positions of the DNA strands. The presence of oxidized bases in fresh sperm could be related to the presence of senescent cells, and could affect DNA sensitivity to cryopreservation as it has been described that oxidized bases could transform directly into DNA breakages increasing fragmentation during freezing-thawing (Box et al 2001, Thomson et al 2009. A higher level of post-thaw DNA strand breaking was effectively detected.…”

Section: Discussionmentioning

confidence: 99%

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Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

Pérez‐Cerezales

Martínez‐Páramo²,

Beirão³

et al. 2010

Reproduction

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Mammalian spermatozoa undergo a strong selection process along the female tract to guarantee fertilization by good quality cells, but risks of fertilization with DNA-damaged spermatozoa have been reported. In contrast, most external fertilizers such as fish seem to have weaker selection procedures. This fact, together with their high prolificacy and external embryo development, indicates that fish could be useful for the study of the effects of sperm DNA damage on embryo development. We cryopreserved sperm from rainbow trout using egg yolk and low-density lipoprotein as additives to promote different rates of DNA damage. DNA fragmentation and oxidization were analyzed using comet assay with and without digestion with restriction enzymes, and fertilization trials were performed. Some embryo batches were treated with 3-aminobenzamide (3AB) to inhibit DNA repair by the poly (ADP-ribose) polymerase, which is an enzyme of the base excision repair pathway. Results showed that all the spermatozoa cryopreserved with egg yolk carried more than 10% fragmented DNA, maintaining fertilization rates of 61.1G2.3 but a high rate of abortions, especially during gastrulation, and only 14.5G4.4 hatching success. Furthermore, after 3AB treatment, hatching dropped to 3.2G2.2, showing that at least 10% DNA fragmentation was repaired. We conclude that trout sperm maintains its ability to fertilize in spite of having DNA damage, but that embryo survival is affected. Damage is partially repaired by the oocyte during the first cleavage. Important advantages of using rainbow trout for the study of processes related to DNA damage and repair during development have been reported. Reproduction (2010) 139 989-997

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

Pérez‐Cerezales

Martínez‐Páramo²,

Beirão³

et al. 2010

Reproduction

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“…Moreover, electron transfer reactions (path C) provide an elegant explanation for the higher yield of 8-oxodGuo formation observed relative to 8-oxodAdo. Through the pioneering work of Box and coworkers (10,12,31,32), the existence of tandem lesions has been described in short oligonucleotides. Here we provide quantitative evidence for the abundance of such lesions in double-stranded DNA exposed to HO…”

Section: Discussionmentioning

confidence: 99%

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Bergeron

Auvré

Radicella

et al. 2010

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

123

113

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Reaction of HO• radicals with double-stranded calf thymus DNA produces high levels of and, to a minor extent, . Formation of the hydroxylated purine lesions is explained by addition of HO • to the C8 position of the purine moiety. It has been reported that tandem lesions containing a formylamine residue neighboring 8-oxodGuo could be produced through addition of a transiently generated pyrimidine peroxyl radical onto the C8 of an adjacent purine base. Formation of such tandem lesions accounted for ≈10% of the total 8-oxodGuo. In the present work we show that addition of HO • onto the C8 of purine accounts for only ∼5% of the generated 8-oxodGuo. About 50% of the 8-hydroxylated purine lesions, including 8-oxodGuo and 8-oxodAdo, are involved in tandem damage and are produced by peroxyl addition onto the C8 of a vicinal purine base. In addition, the remaining 45% of the 8-oxodGuo are produced by an electron transfer reaction, providing an explanation for the higher yield of formation of 8-oxodGuo compared to 8-oxodAdo. Interestingly, we show that >40% of the 8-oxodGuo involved in tandem lesions is refractory to excision by DNA glycosylases. Altogether our results demonstrate that, subsequently to a single oxidation event, peroxidation reactions significantly increase the yield of formation of hydroxylated purine modifications, generating a high proportion of tandem lesions partly refractory to base excision repair.DNA damage | DNA repair | peroxidation reaction | tandem lesions F ormation of oxidatively generated DNA lesions is associated with the occurrence of degenerative diseases, cancer, and aging (1). Therefore, reactions of reactive oxygen species, and among them the highly genotoxic hydroxyl radical (HO • ), with DNA constituents have been extensively studied during the last three decades (2). 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and, to a minor extent the corresponding adenine derivative 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxodAdo), have been shown to be significantly generated in cellular DNA under various conditions of oxidative stress. More than 20 years ago (3) it was established that in the presence of HO• (produced either by the indirect effect of ionizing radiation or by Fenton-type reactions) the mechanism of formation of 8-hydroxylated purine lesions (8-oxoPur), including both 8-oxodGuo and 8-oxodAdo, involves addition of HO• to the C8 position of the purine bases, followed by an oxidation reaction (for a review see refs. 2 and 4). In addition, 8-oxoPur could be also produced by a one-electron oxidation process followed by hydration of the purine radical cation thus generated, producing following oxidation mainly 8-oxodGuo due to efficient charge transfer processes (5, 6) combined with the relatively low ionization potential of guanine compared to other DNA constituents.In addition, the pioneering work of Box and coworkers (7-10) suggested the possible formation of tandem lesions, constituted of two adjacent modifications. Recent works have demonstrated that in dinucleoside monophosp...

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“…Εκτός από τα λιπίδια και τις πρωτεΐνες, τα RONS προσβάλλουν και το DNA προκαλώντας «σπασίματα» στις αλυσίδες του και βλάβες στο μηχανισμό επιδιόρθωσης των βάσεων (Halliwell & Gutteridge, 2007). Από αυτή την δράση των RONS έχουν αναγνωριστεί μέχρι σήμερα αρκετές σημαντικές οξειδωτικές τροποποιήσεις στο DNA (Box, Dawidzik, & Budzinski, 2001). Ένα παραπροϊόν που παράγεται από αυτές τις τροποποιήσεις είναι, η 8-υδροξυδεοξυγουανοσίνη (OH8dG), η οποία προκύπτει από την οξείδωση της γουανίνης στη θέση C8 του πουρινικού δακτυλίου.…”

Section: η δράση της υπεροξειδικής δισμουτάσηςunclassified

“…Ένα παραπροϊόν που παράγεται από αυτές τις τροποποιήσεις είναι, η 8-υδροξυδεοξυγουανοσίνη (OH8dG), η οποία προκύπτει από την οξείδωση της γουανίνης στη θέση C8 του πουρινικού δακτυλίου. Η τροποποίηση της OH8dG δημιουργείται κυρίως από τη δράση του OH • που αντιδρά με τη δεοξυριβόζη αλλά και με τις αζωτούχες βάσεις του DNA (Box, et al, 2001). Παράλληλα, έγινε εφικτή, από τους ίδιους επιστήμονες, και η σύνθεση της βιταμίνης C. Χαρακτηριστικό της βιταμίνης C είναι το ότι τόσο η φυσική της σύνθεση όσο και η συνθετική έχουν τις ίδιες φυσικές και χημικές βιολογικές ιδιότητες.…”

Section: η δράση της υπεροξειδικής δισμουτάσηςunclassified

Η Επίδραση Της Έκκεντρης Προπόνησης Σε Δείκτες Μυϊκής Βλάβης Και Οξειδωτικού Στρες

Θεοδώρου¹

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Anastasios A. Theodorou : The effect of eccentric training on muscle damage and redox status indices (Under the supervision of Athanasios Jamurtas, Assistand Professor)Antioxidant supplementation is quite often among athletes in an attempt to counteract the increased production of free radicals during exercise and especially after exerciseinduced muscle damage (eccentric). Recently an increasing number of studies reported negative effects of antioxidant supplementation on the training and cellular adaptations to chronic exercise. The aim of the present study was to investigate the effects of vitamin C and E supplementation on muscle performance, blood and muscle redox status, hemolysis and blood lipid profile in both trained and untrained individuals after acute and chronic exercise. After previous investigations of our group, a specific type of exercise was applied (eccentric) in order to produce long lasting and extensive changes in all biomarkers and examine more easily any effects of antioxidant supplementation. In a double-blinded fashion, participants received either a daily oral supplementation of vitamin C and vitamin E (n=14) or placebo (n=14) for eleven weeks. Following baseline tests, volunteers performed an eccentric exercise session two times per week for four weeks. Before and after the chronic eccentric exercise volunteers were subjected to one session of acute eccentric exercise, and physiological measurements were performed as well as blood samples and muscle biopsies (from 8 participants) were collected. The present results failed to support any effect of antioxidant supplementation; eccentric exercise similarly modified muscle damage and performance, blood redox status, hemolysis and lipid profile in both supplemented and non-supplemented groups. This is despite the fact that eccentric exercise induced marked changes in muscle damage and performance as well as redox status and lipid profile for several days after exercise. The complete lack of any effect on the physiological and biochemical outcome measures employed questions the validity of using orally antioxidant supplementation as redox modulators of muscle and redox status in healthy humans. Moreover, the lack of any effect of antioxidant supplementation on training and cellural adaptation to exercise observed in this study, opposed previous studies suggesting that antioxidant may block training adaptations.

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Free radical-induced double lesions in DNA

Cited by 131 publications

References 71 publications

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Η Επίδραση Της Έκκεντρης Προπόνησης Σε Δείκτες Μυϊκής Βλάβης Και Οξειδωτικού Στρες

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Free radical-induced double lesions in DNA

Cited by 131 publications

References 71 publications

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

HO • radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Η Επίδραση Της Έκκεντρης Προπόνησης Σε Δείκτες Μυϊκής Βλάβης Και Οξειδωτικού Στρες

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HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases