Ion-Enhanced Conversion of CO2 into Formate on Porous Dendritic Bismuth Electrodes with High Efficiency and Durability.

Invited for this month's cover is the group of Prof. Hyunwoong Park at the Kyungpook National University. The image shows the high-efficiency CO2 conversion to formate using multilayered porous dendrite Bi electrocatalysts. The Full Paper itself is available at 10.1002/cssc.201902581.

Ion-Enhanced Conversion of CO2 into Formate on Porous Dendritic Bismuth Electrodes with High Efficiency and Durability.

Facile synthesis of efficient electrocatalysts that can selectively convert CO2 to value-added chemicals remains a challenge. Herein, the electrochemical synthesis of porous Bi dendrite electrodes and details of their activity toward CO2 conversion to formate in aqueous solutions of bicarbonate are presented. The as-synthesized multilayered, porous, dendritic Bi electrodes exhibit a faradaic efficiency (FE) of approximately 100 % for formate production. Added halides and cations significantly influence the steady-state partial current density for formate production JFM (Cl- >Br- ≈I- ; Cs+ >K+ >Li+ ). DFT calculations revealed that the reaction pathway involving the species *OCOH occurs predominantly and the presence of both Cs+ and Cl- makes the overall reaction more spontaneous. Photovoltaic-cell-assisted electrocatalysis produced formate with an FE of approximately 95 % (JFM ≈10 mA cm-2 ) at an overall solar conversion efficiency of approximately 8.5 %. The Bi electrodes maintain their activity for 360 h without a change in the surface states.

Sunlight-charged heterojunction TiO2 and WO3 particle-embedded inorganic membranes for night-time environmental applications.

A metal oxide-heterojunction photocatalyst is developed to harvest sunlight, store the energy in electrons, and apply the stored energy in water treatment. Light-absorbing nanoparticular and nanotubular TiO2 are hybridized with electron-storing WO3 at different weight ratios of TiO2 to WO3 (e.g., TW25 represents a composite of 25 wt% TiO2 and 75 wt% WO3). The ability of the TW composite to utilize the stored electrons is examined for the reduction of hexavalent chromium (Cr(vi)). In the photoelectrochemical (PEC) tests, irradiation using simulated sunlight (AM 1.5, 100 mW cm-2) leads to a rapid shift in the open-circuit potential (OCP) of the TW electrodes to the negative potential region (photocharging process). The termination of irradiation causes a gradual shift of the OCP to the positive potential region over 20 h (discharging process). Spiked Cr(vi) added to the solution with pre-photocharged TW electrodes is efficiently removed; the kinetics of this process depends on the TW composition (25, 50, or 75 wt%), TiO2 morphology (particular or tubular), initial Cr(vi) concentration (0.125 or 0.25 ppm), and whether the conditions are aerated or non-aerated. Based on this knowledge, TW composite-embedded inorganic membranes are synthesized and charged using sunlight. For Cr(vi) removal, single-pass and continuous circulation filtration systems are employed. The fraction of Cr(vi) removed from the circulation system is ∼30% in 4 h, which is 1.5 times that removed using the single-pass filtration system (∼20%). An X-ray photoelectron spectroscopy analysis of the TW membranes used for Cr(vi) removal reveals that Cr is not sorbed in the membrane. The W(vi) in WO3 is partially reduced to W(6-x)+ upon photocharging and is oxidized during the reduction of Cr(vi), leading to the co-existence of W6+ and W(6-x)+.

Complex formation of a 4-α-glucanotransferase using starch as a biocatalyst for starch modification.

A 4-α-glucanotransferases from Thermus thermophilus (TTαGT) possesses an extra substrate binding site, leading to facile purification of the intact enzyme using amylose as an insoluble binding matrix. Due to the cost of amylose and low recovery yield, starch was replaced for amylose as an alternative capturer in this study. Using gelatinized corn starch at pH 9 with 36-h incubation in the presence of 1 M ammonium sulfate increased the TTαGT-starch complex formation yield from 2 to 56%. In preparative-scale production, TTαGT produced in Bacillus subtilis was recovered by 42.1% with the same specific activity as that of purified TTαGT. Structural and rheological analyses of the enzymatically modified starches revealed that the starch complex exhibited catalytic performance comparable to soluble TTαGT, suggesting that the starch complex can be used as a biocatalyst for modified starch production without elution of the enzyme from the complex.

Overproduction and characterization of a lytic polysaccharide monooxygenase in Bacillus subtilis using an assay based on ascorbate consumption.

Lytic polysaccharide monooxygenases (LPMOs) are copper ion-containing enzymes that degrade crystalline polysaccharides, such as cellulose or chitin, through an oxidative mechanism. To the best of our knowledge, there are no assay methods for the direct characterization of LPMOs that degrade substrates without coupled enzymes. As such, in this study, a coupled enzyme-free assay method for LPMOs was developed, which is based on measuring the consumption of ascorbic acid used as an external electron donor for LPMOs. To establish this new assay method, a chitin-active LPMO from Bacillus atrophaeus (BatLPMO10) was cloned as a model enzyme. An expression system using B. subtilis as the host cell yielded a simple purification process without complicated periplasmic fractionation, as well as improved productivity by 3.7-fold higher than that of Escherichia coli BL21(DE3). At the optimum pH determined using a newly developed assay, BatLPMO10 showed the highest activity in terms of promoting chitin degradation by a chitinase. In addition, the assay method indicated that BatLPMO10 was inhibited by sodium ions, and BatLPMO10 and a chitinase mutually enhanced each other's activities upon degrading chitin as the substrate. In conclusion, this hydrolase-free ascorbate assay allows quantitative analysis of BatLPMO10 without a coupled enzyme.

Anti alpha-gal immune response following porcine bioprosthesis implantation in children.

BACKGROUND AND AIM OF THE STUDY: Porcine bioprostheses have been widely used in cardiac surgery in the treatment of valvular heart disease. However, in younger patients, their use has been limited by early failures known to be associated with an immune response and subsequent degeneration. The natural antibodies directed at Galalpha1, 3-Galbeta1-4GlcNAc-R(alpha-Gal), have been thought to initiate an immune response in humans transplanted with porcine organ xenografts. The study aim was to determine the anti alpha-Gal immune response following commercial porcine bioprosthesis implantation in children. METHODS: Between January 2008 and April 2008, 19 consecutive patients underwent pulmonary valve replacement (PVR) with a commercially available porcine bioprosthesis for an incompetent pulmonary valve with congenital heart diseases. The median age at surgery was 132 months (range: 14-330 months). Previous PVR with a porcine bioprosthesis had been performed in seven patients at a median of 44 months (range: 26-117 months) before surgery (re-PVR group). Sera were obtained sequentially five times: immediately before surgery, and at one day, one week, three weeks, and two months postoperatively. All serum samples were analyzed using an enzyme-linked immunosorbent assay to investigate the alpha-Gal immune response. RESULTS: There were no operative deaths or complications. There was no statistically significant difference between the titers of anti alpha-Gal antibodies of the PVR and re-PVR groups. The titer of anti alpha-Gal antibodies (IgM and IgG) was decreased on the first postoperative day, but increased in the first postoperative week, regardless of the isotype. Whilst the titer of the anti alpha-Gal IgM antibody began to decrease after three weeks postoperatively, the titer of anti alpha-Gal IgG antibody remained increased after two months. CONCLUSION: The implantation of a porcine bioprosthesis elicits the increased formation of anti alpha-Gal antibodies during the early postoperative period in children, with different patterns between the two isotypes. The IgM antibody response was rapid and transient, while the IgG antibody response was longer and more delayed.

p31comet Induces cellular senescence through p21 accumulation and Mad2 disruption.

Functional suppression of spindle checkpoint protein activity results in apoptotic cell death arising from mitotic failure, including defective spindle formation, chromosome missegregation, and premature mitotic exit. The recently identified p31(comet) protein acts as a spindle checkpoint silencer via communication with the transient Mad2 complex. In the present study, we found that p31(comet) overexpression led to two distinct phenotypic changes, cellular apoptosis and senescence. Because of a paucity of direct molecular link of spindle checkpoint to cellular senescence, however, the present report focuses on the relationship between abnormal spindle checkpoint formation and p31(comet)-induced senescence by using susceptible tumor cell lines. p31(comet)-induced senescence was accompanied by mitotic catastrophe with massive nuclear and chromosomal abnormalities. The progression of the senescence was completely inhibited by the depletion of p21(Waf1/Cip1) and partly inhibited by the depletion of the tumor suppressor protein p53. Notably, p21(Waf1/Cip1) depletion caused a dramatic phenotypic conversion of p31(comet)-induced senescence into cell death through mitotic catastrophe, indicating that p21(Waf1/Cip1) is a major mediator of p31(comet)-induced cellular senescence. In contrast to wild-type p31(comet), overexpression of a p31 mutant lacking the Mad2 binding region did not cause senescence. Moreover, depletion of Mad2 by small interfering RNA induced senescence. Here, we show that p31(comet) induces tumor cell senescence by mediating p21(Waf1/Cip1) accumulation and Mad2 disruption and that these effects are dependent on a direct interaction of p31(comet) with Mad2. Our results could be used to control tumor growth.

Mutation analysis of p31comet gene, a negative regulator of Mad2, in human hepatocellular carcinoma.

Failure of mitotic checkpoint machinery leads to the chromosomal missegregation and nuclear endoreduplication, thereby driving the emergence of aneuploidy and tetraploidy population. Although abnormal nuclear ploidy and the resulting impairment of mitotic checkpoint function are typical physiological event leading to human hepatocellular carcinoma, any mutational change of mitotic checkpoint regulators has not yet been discovered. Therefore, we investigated the mutation of p31(comet), a recently identified mitotic checkpoint regulator, in human hepatocellular carcinoma. Of 51 human hepatocellular carcinoma tissue and 6 cell lines tested, five samples exhibited nucleotide sequence variations dispersed on four sites within the entire coding sequence. Among these sites with sequence substitutions, three were found to be missense mutation accompanied with amino acid change but one was a silent mutation. Of these sequence substitutions, two were present in both tumor and non-tumor liver tissues, suggesting the possibility of polymorphism. The present findings indicate that p31(comet) does not have an impact on the formation of aneuploidy and tetraploidy found in human hepatocellular carcinoma.

8-oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein.

8-oxo-7,8-dihydroguanosine triphosphate (8-oxoGTP) has been regarded simply as a oxidative mutagenic byproduct. The results obtained in this study imply that it may act as a down-regulator of respiratory burst of neutrophils. Human neutrophils treated with PMA produced superoxides and at the same time, the cytosol of these cells was intensely immunostained by 8-oxo-7,8-dihydroguanosine(8-oxoG) antibody, indicating that 8-oxoG-containing chemical species including 8-oxoGTP are produced. Human neutrophil lysates treated with PMA also produced superoxides, which was stimulated by GTPgammaS but inhibited by 8-oxoGTPgammaS. Moreover, 8-oxoGTPgammaS suppressed the stimulatory action of GTPgammaS. Likewise, GTPgammaS stimulated Rac activity in neutrophil lysates but 8-oxoGTPgammaS and GDP inhibited it. The inhibitory effect of GDP was one tenth that of 8-oxoGTPgammaS. Here again, 8-oxoGTPgammaS also suppressed the stimulatory action of GTPgammaS on Rac activity. These results imply the possibility that 8-oxoGTP is formed during respiratory burst of neutrophils and limits neutrophil production of superoxides by antagonizing GTP toward Rac.

PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells.

Expression of matrix metalloproteinase-9 (MMP-9) is associated with airway remodeling and tissue injury in asthma. However, little is known about how MMP-9 is up-regulated in airway epithelial cells. In this study, we show that phorbol myristate acetate (PMA) induces MMP-9 expression via a protein kinase Calpha (PKCalpha)-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Go6976, a PKCalpha/beta isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKCalpha antisense oligonuclotides. PMA activated NF-kappaB by phosphorylating IkappaB in these cells and this was also inhibited by GF109203X and Go6976, suggesting that PKCa acts as an upstream regulator of NF-kappaB in PMA-induced MMP-9 induction. Our results indicate that a "PKCalpha-NF- kappaB"-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium.

Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2 cells for the identification of potential biomarkers for PAH monitoring and risk assessment.

To identify potential biomarkers for the monitoring and risk assessment of benzo[a]pyrene (BaP), the oxidative stress-related DNA damage and p53 modification were investigated in human hepatoma HepG2 cells. Benzo[a]pyrene exposure induced a decrease in the cell viability, but increased the antioxidant enzyme activity as well as the DNA and lipid damage. The p53 protein activation appeared to have been a downstream response to the benzo[a]pyrene-induced DNA damage, suggesting p53 plays important roles in the defense against benzo[a]pyrene-induced genotoxicity. The response of phosphorylated p53 may be more sensitive towards benzo[a]pyrene exposure than normal p53. Following DNA damage, the activation of p53 acts as a transcriptional regulator of several target genes, including, p21 protein; a gene that encodes the Cdk inhibitor and is induced by exposure to benzo[a]pyrene. The p53 mRNA level was increased after the treatment of cells with benzo[a]pyrene, as well as following the induction of p53 protein, suggesting the benzo[a]pyrene-stimulated p53 accumulation may also be transcriptionally induced. The overall results suggest that benzo[a]pyrene leads to serious DNA damage, which leads to the transcription of the p53 gene; that the subsequent p53 protein accumulation up-regulates the cellular p21 protein. Oxidative DNA damage and p53 accumulation seem to be related to benzo[a]pyrene toxicity; however, their potential as biomarkers in environmental monitoring and risk assessment needs to be validated in the context of their specificity and sensitivity.

Oh8dG induces G1 arrest in a human acute leukemia cell line by upregulating P21 and blocking the RAS to ERK signaling pathway.

We reported previously that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh8Gua) glycosylase 1 (OGG1) activity and undergoes apoptotic death after treatment with 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodeoxyguanosine, 8-hydroxydeoxyguanosine; oh8dG). In our present study, we further characterized the effects of oh8dG in KG-1 cells and found that, in addition to apoptosis, oh8dG induced the arrest of KG-1 at the G1 phase. Simultaneously, oh8dG-treated KG-1 showed an increase in the oh8Gua content of DNA, upregulation of p21 (an inhibitor of cdk), and Ras inactivation. Moreover, the upregulation of p21 was followed by the inactivations of cdk4 and cdk2, the hypophosphorylation of Rb, and a marked decline in the expression of c-myc (a gene regulated by E2F that is a transcription factor whose activity is suppressed when it is bound to hypophosphorylated Rb). Ras inactivation was also followed by the inactivation of ERK kinase (MEK) and the inactivation of AP-1, a downstream target of the Ras signaling pathway. The specific MEK inhibitors, PD98059 and U0126, also induced G1 arrest. These findings suggest that p21 upregulation and Ras inactivation contribute to G1 arrest. An increase of oh8Gua content in DNA does not seem to be a principal contributor to G1 arrest, however, because the kinetics of increases of oh8Gua content in DNA and of G1 cell number did not coincide. We report that oh8dG induces the arrest of KG-1 growth at the G1 phase mainly by upregulating p21 and inactivating Ras.

STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells.

Aberrantly enhanced vascular endothelial growth factor (VEGF) gene expression is associated with increased tumor growth and metastatic spread of solid malignancies, including human renal carcinomas. Persistent activation of STAT3 is linked to tumor-associated angiogenesis, but underlying mechanisms remain unclear. Therefore, we examined whether STAT3 modulates the stability and activity of hypoxia-inducible factor-1alpha (HIF-1alpha), and in turn enhances VEGF expression. We found that STAT3 was activated in ischemic rat kidneys and hypoxic human renal carcinoma cells. We also found that hypoxia-induced activation of STAT3 transactivated the VEGF promoter and increased the expression of VEGF transcripts. Consistent with these findings, STAT3 inhibition attenuated the hypoxic induction of VEGF. Interestingly, activated STAT3 increased HIF-1alpha protein levels due to the HIF-1alpha stability by blocking HIF-1alpha degradation and accelerated its de novo synthesis. The novel interaction of STAT3 with HIF-1alpha was identified in hypoxic renal carcinoma cells. Furthermore, hypoxia recruited STAT3, HIF-1alpha, and p300 to the VEGF promoter and induced histone H3 acetylation. Therefore, these findings provide compelling evidence that a causal relationship exists between STAT3 activation and HIF-1-dependent angiogenesis and suggest that therapeutic modalities designed to disrupt STAT3 signaling hold considerable promise for the blocking tumor growth and enhancing apoptosis of cancer cells and tissues.

In vitro evidence for the recognition of 8-oxoGTP by Ras, a small GTP-binding protein.

Oxygen radicals attack guanine bases in DNA but they also attack cytoplasmic GTP forming 8-oxoGTP. The presence of 8-oxoGTP in cytoplasm is evidenced by the fact that cells contain MutT/MTH1 which hydrolyze 8-oxoGTP into 8-oxoGMP. In this study, the interaction between 8-oxoGTP and Ras, a small GTP-binding protein, was tested in vitro, and the action of 8-oxoGTP was compared to that of GTP. When purified Ras was treated with 8-oxoGTPgammaS, Ras was activated, as indicated by the enhanced binding of Ras with Raf-1. GTPgammaS also activated Ras but 8-oxoGTPgammaS had a much more potent effect. In lysates of human embryo kidney 293 cells, 8-oxoGTPgammaS activated not only Ras but also the downstream effectors of the Ras-ERK pathway, i.e., Raf-1 and ERK1/2. In contrast to Ras, other small GTP-binding proteins, Rac1 and Cdc42, were inactivated by 8-oxoGTPgammaS, whereas both of these proteins were activated by GTPgammaS, indicating that the biological natures of 8-oxoGTP and GTP differ. These results suggest the possibility that 8-oxoGTP is not a simple by-product but a functional molecule transmitting an oxidative signal to small GTP-binding proteins like Ras.

MutY is down-regulated by oxidative stress in E. coli.

In Escherichia coli, MutM (8-oxoG DNA glycosylase/lyase or Fpg protein), MutY (adenine DNA glycosylase) and MutT (8-oxodGTPase) function cooperatively to prevent mutation due to 7, 8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic oxidative DNA adduct. MutM activity has been demonstrated to be induced by oxidative stress. Its regulation is under the negative control of the global regulatory genes, fur, fnr and arcA. However, interestingly the presence of MutY increases the mutation frequency in mutT- background because of MutY removes adenine (A) from 8-oxoG:A which arises from the misincorporation of 8-oxoG against A during DNA replication. Accordingly we hypothesized that the response of MutY to oxidative stress is opposite to that of MutM and compared the regulation of MutY activity with MutM under various oxidative stimuli. Unlike MutM, MutY activity was reduced by oxidative stress. Its activity was reduced to 30% of that of the control when E. coli was treated with paraquat (0.5mM) or H2O2 (0.1 mM) and induced under anaerobic conditions to more than twice that observed under aerobic conditions. The reduced mRNA level of MutY coincided with its reduced activity by paraquat treatment. Also, the increased activity of MutY in anaerobic conditions was reduced further in E. coli strains with mutations in fur, fnr and arcA and the maximum reduction in activity was when all mutations were present in combination, indicating that MutY is under the positive control of these regulatory genes. Therefore, the down-regulation of MutY suggests that there has been complementary mechanism for its mutagenic activity under special conditions. Moreover, the efficacy of anti-mutagenic action should be enhanced by the reciprocal co-regulation of MutM.

Induction of the differentiation of HL-60 promyelocytic leukemia cells by L-ascorbic acid.

The present study was undertaken to examine the effect of L-ascorbic acid (LAA) on the growth of HL-60 promyelocytic leukemia cells, besides induction of apoptosis. LAA (> or = 10(-4) M) was found to markedly inhibit the proliferation of HL-60 in liquid culture and clonogenicity in semisolid culture. Moreover, LAA-treated HL-60 showed activity to produce chemiluminescence and expressed CD 66b cell surface antigens, indicating that LAA induces the differentiation of HL-60 mainly into granulocytes. The results are supported by morphological changes of LAA-treated HL-60 into segmented neutrophils. Therefore, the inhibitory effect of LAA on the growth of HL-60 cells seems to arise from the induction of differentiation. To assess the potential role of LAA, cells were exposed to oxygen radical scavengers in the absence or presence of LAA. Catalase abolished and superoxide dismutase promoted LAA-induced differentiation of HL-60. Thus, H2O2 produced as a result of LAA treatment seems to play a major role in induction of HL-60 differentiation.

8-hydroxydeoxyguanosine causes death of human leukemia cells deficient in 8-oxoguanine glycosylase 1 activity by inducing apoptosis.

Our previous study showed that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh(8)Gua) glycosylase 1 (OGG1) activity and that its viability is severely affected by 8-hydroxydeoxyguanosine (8-oxodeoxyguanosine; oh(8)dG). In the present study, the nature of the killing action of oh(8)dG on KG-1 was investigated. Signs observed in oh(8)dG-treated KG-1 cells indicated that death was due to apoptosis, as demonstrated by: increased sub-G(1) hypodiploid (apoptotic) cells, DNA fragmentation, and apoptotic body formation; loss of mitochondrial transmembrane potential, the release of cytochrome c from mitochondria into the cytosol, and the down-regulation of bcl-2; and the activation of caspases 8, 9, and 3, and the efficient inhibition of the apoptotic process by caspases inhibitors. This apoptosis appears not to be associated with Fas/Fas ligand because the expressions of these proteins were unchanged. Apoptotic KG-1 cells showed a high concentration of oh(8)Gua in DNA. Moreover, the increased concentration of oh(8)Gua in DNA, and the apoptotic process were not suppressed by the antioxidant, N-acetylcysteine, and thus the process is independent of reactive oxygen species. Of the 18 cancer cell lines treated with oh(8)dG, 3 cell lines (H9, CEM-CM3, and Molt-4) were found to be committed to apoptosis, and all of these showed very low OGG1 activity and a marked increase in the concentration of oh(8)Gua in DNA. These observations indicate that in addition to its mutagenic action, oh(8)Gua in DNA disturbs cell viability by inducing apoptosis.

Measurement of oxidative damage at individual gene levels by quantitative PCR using 8-hydroxyguanine glycosylase (OGG1).

In this study, an attempt was made to develop a method to estimate oxidative damage of individual genes for assessing chemopreventive potential of dietary or medicinal plants. Oxidative damage was investigated on the two genes in gastric mucosal tissue infected with Helicobacter pylori, which were genes of glyceraldehydes-3-phosphate dehydrogenase (GAPDH), a house-keeping gene, and gene of insulin-like growth factor II receptor (IGFIIR), a gene known to be mutated frequently in gastric carcinoma. The oxidative damage in genomic DNA in the above tissue was confirmed by immunohistochemical study using monoclonal antibody to 8-hydroxyguanine (oh(8)G), which showed much higher degree of staining in their nuclei. Using the method we developed, it was demonstrated that the number of oh(8)G (indicated by 8-hydroxyguanine glycosylase (OGG1) sensitive sites) in GAPDH was almost not changed in H. pylori-infected tissue but in IGFIIR, it increased significantly. These results indicate that this method is valid for the estimate of oxidative damage of individual genes and also showed that the susceptibility of genomic DNA to attack of reactive oxygen species is not homogeneous but different depending upon the region of DNA. We expect to use this method in studies of carcinogenic mechanism and chemoprevention since it can provide more specific information pertaining to individual genes we are interested in.

Gene-specific oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa.

To study the status of oxidative DNA damage in Helicobacter pylori infection in more detail, we examined oxidative DNA damage to individual genes by determining the loss of PCR product of a targeted gene before and after gastric mucosal DNA was treated with 8-hydroxyguanine glycosylase, which cleaves DNA at the 8-hydroxyguanine residues. The results showed that, of the 5 genes tested, p53, insulin-like growth factor II receptor and transforming growth factor-beta receptor type II showed significant oxidative DNA damage in H. pylori-positive tissues and that the BAX and beta-ACTIN genes were relatively undamaged. These results suggest that in H. pylori infection, oxidative DNA damage does not occur homogeneously throughout the genomic DNA but, rather, in a gene-specific manner. We conclude that the progressive accumulation of preferential oxidative DNA damage in certain genes, such as p53, likely contributes to gastric carcinogenesis.