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PubMed1994

Biological inactivation of pBR322 plasmid DNA by enzyme- and radiation-induced single-strand damage under various conditions.

The influence of three different kinds of single-strand breaks (ssb) on the biological activity of plasmid DNA (pBR322) was studied. The single-strand breaks were produced either by gamma-irradiation (together with base and sugar damage) or by DNase I digestion which introduced ligatable ssb. Non-ligatable ssb--single-strand gaps of three nucleotides in length--were generated in the nicked DNA by exonuclease III treatment. The biological activity (N/N(o)) of this damaged DNA was assessed in vivo by transformation of E. coli (CMK) repair wild-type cells. The activity of the enzymes of E. coli was studied in vitro by incubation in a protein extract of E. coli making use of an in vitro assay introduced earlier, which makes it possible to distinguish between enzymatic degradation (dsb formation) and repair of damaged plasmid DNA. The biological activity (D37) of DNA with non-ligatable ssb, as determined by electrotransformation, was about 56% lower than that of DNA with ligatable ssb. The biological activity of enzymatically damaged DNA is greater in calcium-treated cells than in electroporated cells. It is proposed that this is due to a calcium-dependent inhibition of nucleases. In contrast to the enzymatically damaged DNA, with gamma-radiation-damaged DNA a calcium-dependent increase in survival was not observed. Therefore, calcium-dependent nucleases do not play a role in the repair of damage produced by gamma-irradiation. The enzyme activity data show that the single-strand damages are either converted into dsb or repaired. A comparison of the efficiency of dsb formation in the extract for two of the single-strand damages is presented. The efficiency depends on the kind of damage and on the presence of cofactors, especially ATP and dNTPs.

Animals↗
PubMed1995

Line shapes and widths of MAS sidebands for 27Al satellite transitions. multinuclear MAS NMR of tugtupite Na8Al2Be2Si8O24Cl2.

A multinuclear 9Be, 23Na, 27Al, and 29Si magic-angle spinning (MAS) NMR study has been performed for the mineral tugtupite (Na8Al2Be2Si8O24Cl2). The extremely well-resolved spectra allow observation of separate spinning sidebands (ssb's) from the inner (+/- 1/2, +/- 3/2) and outer (+/- 3/2, +/- 5/2) 27Al satellite transitions, and are utilized in a detailed analysis of the line shapes and widths of the individual ssb's from simulations. The line widths of the ssb's from the inner and outer 27Al satellite transitions are found to decrease systematically with increasing order of the ssb's across the spectrum. Accurate values for the 9Be, 23Na, and 27Al quadrupole coupling parameters and isotropic chemical shifts are obtained from simulations of the manifolds of ssb's from the satellite transitions. MAS NMR of the 9Be satellite transitions for tugtupite, BeO, and beryl(Al2Be3Si6O18) shows that these transitions are particularly useful for determination of 9Be quadrupole couplings because of the small 9Be quadrupole moment. The 29Si shielding anisotropy of delta sigma = 48 ppm in tugtupite is the largest determined so far for a framework SiO4 tetrahedron. Finally, the crystal structure of the tugtupite sample has been refined by single-crystal X-ray diffraction, and correlations between the multinuclear NMR parameters and structural data are reported.

Crystallization↗
PubMedDate not supplied

DNA damage in peripheral lymphocytes of untreated breast cancer patients.

BACKGROUND: Using the alkaline comet assay, DNA single-strand breaks (ssb) have been described in peripheral blood lymphocytes (PBL) from breast cancer patients without treatment, but there is no information concerning the occurrence of double-strand breaks (dsb) in the same patients. The purpose of this study was to investigate whether PBL of untreated sporadic breast cancer patients harbor an elevated number of both DNA strand breaks. METHODS: Forty breast cancer patients without family history of cancer in clinical stage III devoid of treatment and 60 age-matched healthy subjects without history of breast cancer were included. PBL from freshly drawn blood were processed following two different methods: the alkaline and the neutral comet assay. Percentage and tail moment were assessed under fluorescence microscopy and a computer-based image analysis system. RESULTS: In controls, ssb were found in 18 +/- 4.67% of PBL, and dsb at 7.99 +/- 3.67% of PBLs. Cancer patients had higher values of both ssb 24.08 +/- 4.96 (p <0.05) and dsb 13.11 +/- 3.2% (p <0.01). Tail moment for ssb was 6.23 +/- 1.44 and dsb, 2.31 +/- 1.09 for controls. For breast cancer patients, tail moment for ssb was 11.73 +/- 2.40 and for dsb, 6.33 +/- 1.75 (p <0.01). On plotting individual measurements of comet percentage against tail moment for alkaline and neutral comet assays, clear separation of control group from cancer patients can be seen in both assays. CONCLUSIONS: Demonstration of two types of DNA damage in PBL of breast cancer patients devoid of treatment or without exposure to environmental genotoxic agents provides a better picture of the degree of DNA damage present in somatic cells of these patients.

Breast Neoplasms↗
PubMed2005

DNA damage detection by an archaeal single-stranded DNA-binding protein.

Archaeal DNA repair pathways are not well defined; in particular, there are no convincing candidate proteins for detection of DNA mismatches or the bulky lesions removed by excision repair pathways. Single-stranded DNA-binding proteins (SSBs) play a central role in DNA replication, recombination and repair. The crenarchaeal SSB is a monomer with a single oligonucleotide-binding fold for single-stranded DNA binding coupled to a flexible C-terminal tail reminiscent of bacterial SSB that mediates interactions with other proteins. We demonstrate that Sulfolobus solfataricus SSB can melt DNA containing a mismatch or DNA lesion specifically in vitro. We suggest that a potential role for SSB in archaea is the detection of DNA damage due to local destabilisation of the DNA double helix, followed by recruitment of specific repair proteins. Proteins interacting specifically with a single-stranded DNA:SSB complex include several known or putative DNA repair proteins and DNA helicases.

Archaeal Proteins↗
PubMed2006

Expression, purification and biochemical characterization of a single-stranded DNA binding protein from Herbaspirillum seropedicae.

An open reading frame encoding a protein similar in size and sequence to the Escherichia coli single-stranded DNA binding protein (SSB protein) was identified in the Herbaspirillum seropedicae genome. This open reading frame was cloned into the expression plasmid pET14b. The SSB protein from H. seropedicae, named Hs_SSB, was overexpressed in E. coli strain BL21(DE3) and purified to homogeneity. Mass spectrometry data confirmed the identity of this protein. The apparent molecular mass of the native Hs_SSB was estimated by gel filtration, suggesting that the native protein is a tetramer made up of four similar subunits. The purified protein binds to single-stranded DNA (ssDNA) in a similar manner to other SSB proteins. The production of this recombinant protein in good yield opens up the possibility of obtaining its 3D-structure and will help further investigations into DNA metabolism.

Amino Acid Sequence↗
PubMed1996

TCDD, endrin and lindane induced oxidative stress in fetal and placental tissues of C57BL/6J and DBA/2J mice.

The abilities of TCDD, endrin and lindane to induce oxidative stress in fetal and placental tissues have been studied after the oral administration of these xenobiotics to pregnant C57BL/6J and DBA/2J mice. Production of superoxide anion, lipid peroxidation and DNA-single strand breaks (SSB) was determined in live fetal and placental tissues 48 hr after administration of single teratogenic doses of the compounds on day 12 of gestation. Oxidative stress and its biomarkers were also determined in livers of day 18 fetuses after administration on day 12 of gestation. TCDD given at doses of 30 and 60 micrograms/kg body weight to the C57BL/6J and DBA/2J mice, respectively, produced increases of 1.3-2.7-fold in superoxide anion production, 1.6-1.9-fold in lipid peroxidation and 2.1-4.4-fold in DNA-SSB. Endrin, given at a dose of 4.5 mg/kg body weight to C57BL/6J and DBA/2J mice, produced increases of 1.3-2.8-fold in superoxide production, 1.4-1.8-fold in lipid peroxidation and 1.4-4.7-fold in DNA-SSB. Lindane when given at a dose of 30 mg/kg body weight to C57BL/6J and DBA/2J mice produced increases of 1.6-3.0-fold in superoxide production, 1.3-2.1-fold in lipid peroxidation and 1.4-5.0-fold in DNA-SSB. The results suggest that superoxide production, lipid peroxidation and DNA-SSB in fetal and placental tissues may participate in the fetotoxic effects of TCDD and other polyhalogenated cyclic hydrocarbons, and that TCDD-induced oxidative damage in fetal and placental tissues is mediated at least in part by the Ah-receptor. The results also indicate that TCDD as an inducer of oxidative tissue damage in the embryos and placentas is approximately 150 and 1000 times more potent than endrin and lindane, respectively, in C57BL/6J mice, and 75 and 500 times more potent than endrin and lindane, respectively, in the DBA/2J mouse strain.

Administration, Oral↗
PubMed1999

Association of redox-active iron bound to high molecular weight structures in nuclei with inhibition of cell growth by H2O2.

Perturbations to Fe species contributing to generation of DNA single-strand breaks (SSBs) and inhibition of growth by H2O2 were studied in HL-60 cells made Fe-deficient by 24 h pretreatment with 144 microM bathophenanthroline disulfonic acid and 400 microM ascorbic acid (Free Radic. Biol. Med. 20: 399; 1996). The diffusion distance for SSB generation (d) in Fe-deficient cells, measured via inhibition with the *OH scavenger Me2SO using alkaline elution, was 6.5 nm. This is similar to the d for Fe-normal cells reported previously. After 1 and 3 h in fresh RPMI 1640 medium containing 10% serum, SSB generation increased from 29 to 56 and 93% of control Fe-normal cells, respectively. The d of the major contributor to SSB generation at these two treatment times was 1.9 nm. This d resembled the d for Fe-ATP as determined in isolated Ehrlich cell nuclei. The association of ATP with Fe2+ was further supported by decreased SSB generation in cells in which ATP synthesis was inhibited. In contrast to SSB generation, H2O2-induced inhibition of growth of Fe-deficient cells treated immediately after placing in fresh medium was not appreciably different from Fe-normal cells. However, after 3 h, an approximately 70% greater concentration of H2O2 than for control, Fe-normal cells was required to inhibit growth. This increase in H2O2 concentration was associated with decreased generation of SSBs by H2O2 in isolated HL-60 cell nuclei. Thus, Fe bound to nuclear structures is more closely associated with inhibition of cell growth than apparent Fe-ATP species. In parallel experiments, changes in total cellular Fe assayed by ashing and complexing with ferrozine were consistent with a non-transferrin mode of acquisition. These short-term changes appear due to processes accompanying reestablishment of the Fe content and distribution normally observed during long-term growth.

Adenosine Triphosphate↗
PubMed1984

Escherichia coli single-stranded DNA binding protein is mobile on DNA: 1H NMR study of its interaction with oligo- and polynucleotides.

The interaction of the Escherichia coli single-stranded DNA binding protein (SSB) with oligo- and poly-nucleotides has been studied by 270-MHz 1H NMR spectroscopy and fast kinetic techniques. d(pT)8 and poly(dT) were used to study noncooperative and cooperative binding, respectively. The H6, H1', and CH3 resonances of d(pT)8 are high-field shifted by less than 0.05 ppm, and H8 and H2 of poly(dA) are low-field shifted upon complexation. The protein resonances remain virtually unshifted. The small shifts upon complexation provide no evidence for extensive stacking interactions between the nucleotide bases and aromatic amino acid side chains of SSB. The d(pT)8 and poly(dA) signals are broadened to about 30 Hz whereas the resonances of poly(dT) are broadened beyond detection upon stoichiometric complexation. Continuous broadening of all poly(dT) signals even at a 10-fold excess of poly(dT) indicates fast exchange of SSB between different binding sites. Dissociation and reassociation rates determined from stopped-flow experiments are too slow by at least 2 orders of magnitude to account for the experimental line widths. Therefore, we conclude that SSB translocates without dissociation from the DNA template. A model for the translocation is outlined. It is based on partial dissociation of octamer sections of poly(dT) from the complex with a rate constant as previously published for the dissociation of d(pT)8 from SSB.

DNA-Binding Proteins↗
PubMed1986

Escherichia coli single-strand binding protein forms multiple, distinct complexes with single-stranded DNA.

Four distinct binding modes for the interaction of Escherichia coli single-strand binding (SSB) protein with single-stranded (ss) DNA have been identified on the basis of quantitative titrations that monitor the quenching of the SSB protein fluorescence upon binding to the homopolynucleotide poly(dT) over a range of MgCl2 and NaCl concentrations at 25 and 37 degrees C. This is the first observation of multiple binding modes for a single protein binding to DNA. These results extend previous studies performed in NaCl (25 degrees C, pH 8.1), in which two distinct SSB-ss DNA binding modes possessing site sizes of 33 and 65 nucleotides per bound SSB tetramer were observed [Lohman, T.M., & Overman, L. B. (1985) J. Biol. Chem. 260, 3594-3603]. Each of these binding modes differs in the number of nucleotides occluded upon interaction with ss DNA (i.e., site size). Along with the previously observed modes with site sizes of 35 +/- 2 and 65 +/- 3 nucleotides per tetramer, a third distinct binding mode, at 25 degrees C, has been identified, possessing a site size of 56 +/- 3 nucleotides per bound SSB tetramer, which is stable over a wide range of MgCl2 concentrations. At 37 degrees C, a fourth binding mode is observed, possessing a site size of 40 +/- 2 nucleotides per tetramer, although this mode is observable only over a small range of salt concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA, Single-Stranded↗
PubMed2006

An investigation into the mechanisms of DNA strand breakage by direct ionization of variably hydrated plasmid DNA.

The mechanisms by which ionizing radiation directly causes strand breaks in DNA were investigated by comparing the chemical yield of DNA-trapped free radicals to the chemical yield of DNA single strand break (ssb) and double strand break (dsb), as a function of hydration (Gamma). Solid-state films of plasmid pUC18, hydrated to 2.5 < Gamma < 22.5 mol, were X-irradiated at 4 K, warmed to room temperature, and dissolved in water. Free radical yields were determined by EPR at 4 K. With use of the same samples, Gel electrophoresis was used to measure the chemical yield of total strand breaks, which includes prompt plus heat labile ssb; G'total(ssb) decreased from 0.092 +/- 0.016 micromol/J at Gamma= 2.5 to 0.066 +/- 0.008 micromol/J at Gamma= 22.5. Most provocative is that at Gamma= 2.5 the yield of total ssb exceeds the yield of trapped deoxyribose radicals: G'total(ssb) - G'sugar(fr) = 0.06 +/- 0.02 micromol/J. Nearly 2/3 of the strand breaks are derived from precursors other than radicals trapped on the deoxyribose moiety. To account for these nonradical precursors, we hypothesize that strand breaks are produced by two one-electron oxidations at a single deoxyribose residue within an ionization cluster.

DNA↗
PubMed1995

The reductive conversion of chromium (VI) by ascorbate gives rise to apurinic/apyrimidinic sites in isolated DNA.

The formation of apurinic/apyrimidinic sites (AP-sites) and single strand breaks (SSB) by chromate and ascorbate (AsA) in isolated DNA was investigated using a number of agents that cleave DNA at AP-sites (putrescine, exonuclease III, the tripeptide Lys-Trp-Lys, and an AP-endonuclease containing fraction isolated from human fibroblasts). Relative to the number of SSB caused by chromate and AsA alone, all these agents induced additional nicking, indicating the induction of AP-sites. Chromate/AsA-induced AP-sites contain aldehyde groups, as cleavage by putrescine could be prevented by treatment with borohydride which reduced the aldehyde. The time course for the formation of both DNA lesions was very similar, and there was a 1:1 ratio of the number of SSB to the number of AP-sites. The addition of catalase to incubation mixtures containing chromate/AsA led to an almost complete suppression of AP-sites and SSB. In systems containing lower concentrations of chromate/AsA, the exclusion of oxygen inhibited the formation of both lesions. It is suggested that AP-sites and SSB arise from attack by reactive species deriving from chromate/AsA on one single site at DNA, probably the sugar moiety. In view of the known mutagenicity of AP-sites, these results could aid an understanding of the mechanisms underlying chromium(VI) carcinogenicity.

Ascorbic Acid↗
PubMed2001

Multicentre, randomised controlled trial of four-layer bandaging versus short-stretch bandaging in the treatment of venous leg ulcers.

BACKGROUND: Aim of the study was to compare the healing rates of venous ulcers obtained with four-layer bandages (4LB) versus short stretch bandages (SSB). DESIGN: Multicentre, randomised controlled trial performed in 5 centres of the Netherlands and in 2 centres in Austria ("PADS-study" = Profore Austrian Dutch Study). PATIENTS AND METHODS: 112 patients (53 treated with 4LB and 59 treated with SSB) completed at least one post-treatment follow-up, 90 completed the study. Bandaging and ulcer assessment was performed at weekly intervals. Randomisation was carried out for each centre and was stratified according to the size (more or less than 10 cm2) of the ulcerated area. Local therapy consisted of plain absorbing, non-adherent dressings. Time to complete healing was recorded up to a maximum of 16 weeks. The two treatment-groups were comparable regarding their baseline-characteristics. RESULTS: In total 33/53 (62%) of ulcer-patients were healed in the 4LB group, compared with 43/59 (73%) in the SSB group (difference 11%, 95% CI -28% to 7%). 77% of the ulcers with an initial area less than 5 cm2 healed as compared with 33% of the larger ulcers. The different healing rates in the centres could be explained by the different sizes of the treated ulcers. Based on Kaplan-Meier estimates the median healing time was 57 days for the 4LB (95% CI 47-85 days) and 63 days for the SSB (95% CI 43-70 days). CONCLUSION: The ulcer healing rate and the median healing time did not differ among the two types of bandages. The main discriminant criterion for healing was the initial ulcer size. In centres who are experienced users of short-stretch bandages, no statistically significant different healing rates of venous ulcers could be found after 4LB or SSB.

Adult↗
PubMed2004

Formation, maintenance and consequences of the imprint at the mating-type locus in fission yeast.

Mating-type switching in the fission yeast Schizosaccharomyces pombe is initiated by a strand-specific imprint located at the mating-type (mat1) locus. We show that the imprint corresponds to a single-strand DNA break (SSB), which is site- but not sequence-specific. We identified three novel cis-acting elements, involved in the formation and stability of the SSB. One of these elements is essential for a replication fork pause next to mat1 and interacts in vivo with the Swi1 protein. Another element is essential for maintaining the SSB during cell cycle progression. These results suggest that the DNA break appears during the S-phase and is actively protected against repair. Consequently, during the following round of replication, a polar double-strand break is formed. We show that when the replication fork encounters the SSB, the leading-strand DNA polymerase is able to synthesize DNA to the edge of the SSB, creating a blunt-ended recombination intermediate.

Cell Cycle↗
PubMed1999

Cloning, over-expression and biochemical characterization of the single-stranded DNA binding protein from Mycobacterium tuberculosis.

The single-stranded DNA binding protein (SSB) plays an important role in DNA replication, repair and recombination. To study the biochemical properties of SSB from Mycobacterium tuberculosis (MtuSSB), we have used the recently published genome sequence to clone the ssb open reading frame by PCR and have developed an overexpression system. Sequence comparison reveals that the MtuSSB lacks many of the highly conserved amino acids crucial for the Escherichia coli SSB (EcoSSB) structure-function relationship. A highly conserved His55, important for homotetramerization of EcoSSB is represented by a leucine in MtuSSB. Similarly, Trp40, Trp54 and Trp88 of EcoSSB required for stabilizing SSB-DNA complexes are represented by Ile40, Phe54 and Phe88 in MtuSSB. In addition, a group of positively charged amino acids oriented towards the DNA binding cleft in EcoSSB contains several nonconserved changes in MtuSSB. We show that in spite of these changes in the primary sequence MtuSSB is similar to EcoSSB in its biochemical properties. It exists as a tetramer, it has the same minimal size requirement for its efficient binding to DNA and its binding affinity towards DNA oligonucleotides is indistinguishable from that of EcoSSB. Furthermore, MtuSSB interacts with DNA in at least two distinct modes corresponding to the SSB35 and SSB56/65 modes of EcoSSB interaction with DNA. However, MtuSSB does not form heterotetramers with EcoSSB. MtuSSB therefore presents us with an interesting system with which to investigate further the role of the conserved amino acids in the biological properties of SSBs.

Amino Acid Sequence↗
PubMed2001

The ratio of single- to double-strand DNA breaks and their absolute values determine cell death pathway.

Bleomycin is a cytotoxic antibiotic that generates DNA double-strand breaks (DSB) and DNA single-strand breaks (SSB). It is possible to introduce known quantities of bleomycin molecules into cells. Low amounts kill the cells by a slow process termed mitotic cell death, while high amounts produce a fast process that has been termed pseudoapoptosis. We previously showed that these types of cell death are a direct consequence of the DSB generated by bleomycin. Here, we use deglyco-bleomycin, a bleomycin derivative lacking the carbohydrate moiety. Although this molecule performs the same nucleophilic attacks on DNA as bleomycin, we show that deglyco-bleomycin is at least 100 times less toxic to Chinese hamster fibroblasts than bleomycin. In fact, deglyco-bleomycin treatment results in apoptosis induction. In contrast, however, deglyco-bleomycin was found to generate almost exclusively SSB. Our results suggest that more than 150 000 SSB per cell are required to trigger apoptosis in Chinese hamster fibroblasts and that SSB are 300 times less toxic than DSB. Taken together with previous studies on bleomycin, our data demonstrates that cells can die by apoptosis, mitotic cell death, or pseudoapoptosis, depending on the number of DNA breaks and on the ratio of SSB to DSB.

Animals↗
PubMed2002

The in vivo function of the ribosome-associated Hsp70, Ssz1, does not require its putative peptide-binding domain.

Two proteins of the Hsp70 class (Ssb and Ssz1) and one of the J-type class (Zuo1) of molecular chaperones reside on the yeast ribosome, with Ssz1 forming a stable heterodimer with Zuo1. We designed experiments to address the roles of these two distantly related ribosome-associated Hsp70s and their functional relationship to Zuo1. Strains lacking all three proteins have the same phenotype as those lacking only one, suggesting that these chaperones all function in the same pathway. The Hsp70 Ssb, whose peptide-binding domain is essential for its in vivo function, can be crosslinked to nascent chains on ribosomes that are as short as 54 amino acids, suggesting that Ssb interacts with nascent chains that extend only a short distance beyond the tunnel of the ribosome. A ssz1 mutant protein lacking its putative peptide-binding domain allows normal growth. Thus, binding of unfolded protein substrates in a manner similar to that of typical Hsp70s is not critical for Ssz1's in vivo function. The three chaperones are present in cells in approximately equimolar amounts compared with ribosomes. The level of Ssb can be reduced only a few-fold before growth is affected. However, a 50- to 100-fold reduction of Ssz1 and Zuo1 levels does not have a substantial effect on cell growth. On the basis of these results, we propose that Ssbs function as the major Hsp70 chaperone for nascent chains on the ribosome, and that Ssz1 has evolved to perform a nonclassical function, perhaps modulating Zuo1's ability to function as a J-type chaperone partner of Ssb.

Animals↗
PubMed2001

Chimeras between single-stranded DNA-binding proteins from Escherichia coli and Mycobacterium tuberculosis reveal that their C-terminal domains interact with uracil DNA glycosylases.

Uracil, a promutagenic base in DNA can arise by spontaneous deamination of cytosine or incorporation of dUMP by DNA polymerase. Uracil is removed from DNA by uracil DNA glycosylase (UDG), the first enzyme in the uracil excision repair pathway. We recently reported that the Escherichia coli single-stranded DNA binding protein (SSB) facilitated uracil excision from certain structured substrates by E. coli UDG (EcoUDG) and suggested the existence of interaction between SSB and UDG. In this study, we have made use of the chimeric proteins obtained by fusion of N- and C-terminal domains of SSBs from E. coli and Mycobacterium tuberculosis to investigate interactions between SSBs and UDGs. The EcoSSB or a chimera containing its C-terminal domain interacts with EcoUDG in a binary (SSB-UDG) or a ternary (DNA-SSB-UDG) complex. However, the chimera containing the N-terminal domain from EcoSSB showed no interactions with EcoUDG. Thus, the C-terminal domain (48 amino acids) of EcoSSB is necessary and sufficient for interaction with EcoUDG. The data also suggest that the C-terminal domain (34 amino acids) of MtuSSB is a predominant determinant for mediating its interaction with MtuUDG. The mechanism of how the interactions between SSB and UDG could be important in uracil excision repair pathway has been discussed.

Binding Sites↗
PubMed2004

Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage: repair balance in human lymphocytes.

Epidemiological evidence has shown that the habitual consumption of diets high in fruits and vegetables is associated with reduced risk of cancers. The challenge is to identify causal mechanisms of effect. The aim of the current study was to determine whether an increase in rate of removal of DNA single-strand breaks (SSB) following oxidative challenge could be provoked ex vivo in peripheral blood lymphocytes (PBL). The PBL were isolated from apparently healthy volunteers following dietary intervention with: (1) a mixed carotene capsule; (2) a daily portion of cooked minced carrots; (3) a matched placebo; (4) a portion of mandarin oranges; (5) vitamin C tablets. Single-cell gel electrophoresis was employed to measure baseline levels of SSB and DNA susceptibility to oxidative damage, and to monitor the number of SSB over 4 h, in both unchallenged and H2O2-treated PBL. The enzymatic capacity for repair of different types of DNA oxidative lesions was also measured using two related cell-free assays. There was no evidence that any of the dietary supplementation regimens altered baseline levels of SSB, provided any direct antioxidant protection or altered DNA repair capacity, with two exceptions: the number of SSB following exposure to H2O2 decreased more rapidly in PBL from volunteers given the mixed carotene capsules and repair patch synthesis activity in PBL increased from volunteers given the cooked carrots. These results suggest that carotenoids and carotenoid-rich foods can influence DNA damage:repair by modulation of discrete stages in the DNA repair mechanisms.

Adolescent↗