PubMed Health⌕ Search

Biomedical subjects

Ryszard Olinski

Publications and source records attributed to Ryszard Olinski.

At least 19 recordsLinked to original sources
PubMed2007

Oxidative damage to DNA and antioxidant status in aging and age-related diseases.

Aging is a complex process involving morphologic and biochemical changes in single cells and in the whole organism. One of the most popular explanations of how aging occurs at the molecular level is the oxidative stress hypothesis. Oxidative stress leads in many cases to an age-dependent increase in the cellular level of oxidatively modified macromolecules including DNA, and it is this increase which has been linked to various pathological conditions, such as aging, carcinogenesis, neurodegenerative and cardiovascular diseases. It is, however, possible that a number of short-comings associated with gaps in our knowledge may be responsible for the failure to produce definite results when applied to understanding the role of DNA damage in aging and age-related diseases.

Adolescent↗
PubMed2007

Higher leukocyte 8-oxo-7,8-dihydro-2'-deoxyguanosine and lower plasma ascorbate in aging humans?

Is oxidative damage of DNA responsible for physiological changes associated with aging? The authors note a positive correlation between the age of human subjects with the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in leukocyte DNA. The levels of urinary 8-oxo-7,8-dihydroguanine and 8-oxodG followed the same pattern of correlation. Age-dependent decline in the concentration of plasma vitamin C was also evident. These interesting observations in humans point towards the need to scrutinize in detail the role of oxidative DNA damage and compromised antioxidant defense systems in age-related physiological disorders.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Severe oxidatively damaged DNA after cisplatin treatment of cancer patients.

There is growing evidence suggesting that cytotoxic activity of cisplatin is closely associated with increased generation of reactive oxygen species (ROS). Therefore, this study was undertaken to examine oxidative DNA damage, which arises as a result of chemotherapy with cisplatin. Using HPLC prepurification/isotope dilution GC/MS methodology, we examined the amount of 8-oxoGua and 8-oxodG excreted into urine in cancer patients (n = 66) who received chemotherapy with cisplatin. One day after the infusion of the drug, significant increase in the amount of 8-oxoGua and 8-oxodG in urine of the patients was observed, when compared to the initial value (78%, p < 0.0001 and 22%, p = 0.0051). In the "nadir days" (when the most distinct cell death based on hematological cell counts can be observed), the level of modified base and nucleoside decreased in comparison with the aforementioned time point. These results, for the first time, indicate that oxidatively damaged DNA may be, at least in part, responsible for cisplatin induced cytotoxicity. Our results also demonstrate that cell death does not contribute to urinary 8-oxoGua and 8-oxodG in humans.

Antineoplastic Agents↗
PubMed2006

Evidence for attenuated cellular 8-oxo-7,8-dihydro-2'-deoxyguanosine removal in cancer patients.

Measurement of the products of oxidatively damaged DNA in urine is a frequently used means by which oxidative stress may be assessed non-invasively. We believe that urinary DNA lesions, in addition to being biomarkers of oxidative stress, can potentially provide more specific information, for example, a reflection of repair activity. We used high-performance liquid chromatography prepurification, with gas chromatography-mass spectrometry (LC-GC-MS) and ELISA to the analysis of a number of oxidative [e.g., 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydro-guanine, 5-(hydroxymethyl)uracil], non-oxidative (cyclobutane thymine dimers) and oligomeric DNA products in urine. We analysed spot urine samples from 20 healthy subjects, and 20 age- and sex-matched cancer patients. Mononuclear cell DNA 8-oxodG levels were assessed by LC-EC. The data support our proposal that urinary DNA lesion products are predominantly derived from DNA repair. Furthermore, analysis of DNA and urinary 8-oxodG in cancer patients and controls suggested reduced repair activity towards this lesion marker in these patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Helicobacter pylori infection is associated with oxidatively damaged DNA in human leukocytes and decreased level of urinary 8-oxo-7,8-dihydroguanine.

Helicobacter pylori infection is responsible for inflammation, increased production of reactive oxygen species and oxidatively damaged DNA in the gastric mucosa. There is also evidence which suggests that H.pylori infection may lead to the development of several extragastroduodenal pathologies with reactive oxygen species involvement. In order to assess whether the infection may impose oxidatively damaged DNA not only in the target organ (stomach) but in other organs as well we decided, for the first time, to analyse the two kinds of oxidatively damaged DNA biomarkers: urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) as well as the level of oxidatively damaged DNA in leukocytes. Using high performance liquid chromatography prepurification/gas chromatography with isotope dilution mass detection methodology, we examined the amount of oxidatively damaged DNA products excreted into urine and the amount of 8-oxodG in the DNA of leukocytes' (with the the HPLC/EC technique) in three groups of children: (i) control group, (ii) H.pylori infected children and (iii) children with gastritis where H.pylori infection was excluded. The levels of 8-oxodG in DNA isolated from leukocytes of H.pylori infected patients and in the group with gastritis without H.pylori infection were significantly higher than in DNA isolated from the control group. The mean level of 8-oxoGua in urine samples of children infected with H.pylori was significantly lower than in the urine of the group with gastritis without H.pylori infection. The data suggest that inflammation itself, not just H.pylori infection, is responsible for the observed rise of 8-oxodG level in leukocytes. However, the observed decrease in the level of modified base in urine seems to be specific for H.pylori infection and possibly linked with nitric oxide mediated inhibition of a key base excision repair enzyme (human 8-oxo-7, 8-dihydroguanine glycosylase) responsible for the repair of 8-oxo-7,8-dihydroguanine.

Adolescent↗
PubMed2005

Does measurement of oxidative damage to DNA have clinical significance?

Oxidative damage to DNA is the seemingly inevitable consequence of cellular metabolism. Furthermore, despite protective mechanisms, cellular levels of damage may increase under conditions of oxidative stress, arising from exposure to a variety of physical or chemical insults. Elevated levels of oxidatively damaged DNA have been measured in numerous diseases, and as a result, it has been hypothesised that such damage plays an integral role in the aetiology of that disease. This review examines the validity of this hypothesis, exploring the mechanisms by which oxidative DNA damage may lead to disease. We conclude that further validation of biomarkers of oxidative DNA damage, along with further elucidation of the role of damage in disease, may allow these biomarkers to become potentially useful clinical tools.

Biomarkers↗
PubMed2005

DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine.

The repair of oxidatively damaged DNA is integral to the maintenance of genomic stability, and hence prevention of a wide variety of pathological conditions, such as aging, cancer and cardiovascular disease. The ability to non-invasively assess DNA repair may provide information regarding repair pathways, variability in repair capacity, and susceptibility to disease. The development of assays to measure urinary DNA lesions offered this potential, although it rapidly became clear that possible contribution from diet and cell turnover may influence urinary lesion levels. Whilst early studies attempted to address these issues, up until now, much of the data appears conflicting. However, recent work from our laboratories, in which human volunteers were fed highly oxidatively modified 15N-labelled DNA demonstrates that diet does not appear to contribute to urinary levels of 8-hydroxyguanine and 7,8-dihydro-8-oxo-2'-deoxyguanosine. Furthermore, we propose that a number of literature reports form an argument against a contribution from cell death. Indeed we, and others, have presented evidence, which strongly suggests the involvement of cell death to be minimal. Taken together, these data would appear to rule out various confounding factors, leaving DNA repair pathways as the principal source of urinary purine, if not DNA, lesions enabling such measurements to be used as indicators of repair.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Oxidative DNA damage and antioxidant vitamin level: comparison among lung cancer patients, healthy smokers and nonsmokers.

In the present study, we examined whether the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in leukocyte DNA is higher in lung cancer patients compared to controls. Factors that may influence oxidative stress, such as antioxidant vitamins, were also determined. These parameters were analyzed in 4 groups of subjects: smokers with lung cancer, ex-smokers with lung cancer, healthy smokers with comparable smoking status and healthy nonsmokers. The 8-oxodGuo mean level in leukocytes of lung cancer patients reached values of 9.22/10(6) dGuo molecules (smokers) and 11.16/10(6) dGuo molecules (ex-smokers). These values were significantly higher than in DNA of healthy smokers and nonsmokers, where mean levels reached 6.99/10(6) dGuo molecules and 5.98/10(6) dGuo molecules, respectively. Mean levels of vitamin C in the plasma of controls and lung cancer patients were 56.17 microM (nonsmokers), 26.34 microM (healthy smokers), 23.83 microM (cancer patients, smokers) and 29.19 microM (cancer patients, ex-smokers). The difference between nonsmokers and the 3 other groups was statistically significant. Vitamin E level was significantly reduced in the plasma of cancer patients (smokers 19.94 microM, ex-smokers 19.59 microM) compared to healthy smokers (28.93 microM). No changes in vitamin A concentration were found. Our results suggest that a high level of 8-oxodGuo in leukocyte DNA and a low concentration of vitamin E in the blood may predict lung cancer risk. However, it is also possible that these phenomena may simply result from disease development.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Substantial decrease of urinary 8-oxo-7,8-dihydroguanine, a product of the base excision repair pathway, in DNA glycosylase defective mice.

Genome integrity is maintained via removal (repair) of DNA lesions and an increased load of such DNA damage has been linked to numerous pathological conditions, including carcinogenesis and ageing. 8-Oxo-7,8-dihydroguanine is one of the most critical lesions of this type. The free 8-oxo-7,8-dihydroguanine produced by the action of a specific DNA glycosylase is a potential source of this compound in urine. To date, there has been no direct, experimental evidence demonstrating that urinary 8-oxo-7,8-dihydroguanine is produced by the base excision repair pathway. For clarification of this issue, we applied a recently developed methodology which involved high performance liquid chromatography pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection to compare the urinary excretion rate of 8-oxo-7,8-dihydroguanine in wild type and OGG1 glycosylase knock out mice. Our study revealed a 26% reduction in urinary level of 8-oxo-7,8-dihydroguanine in OGG1 deficient mice in comparison with the wild type strain. This clearly indicates that the mouse OGG1 glycosylase contributes significantly to the generation of urinary 8-oxo-7,8-dihydroguanine. Therefore, urinary measurements of 8-oxo-7,8-dihydroguanine may be attributed to DNA damage and repair, which in turn suggests that they may be useful in studying associations between DNA repair and disease.

Animals↗
PubMed2004

Urinary excretion of DNA repair products correlates with metabolic rates as well as with maximum life spans of different mammalian species.

Using recently developed methodology, which includes HPLC prepurification followed by GC/MS with isotope dilution, we analyzed urinary excretion of possible repair products of oxidative DNA damage-8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and 5-(hydroxymethyl)uracil (5-HMUra)-in mammalian species that substantially differ in metabolic rate and longevity, namely, mice, rats, rabbits, dogs, pigs, and humans. We found highly significant, positive correlations between specific metabolic rates of the animals studied and their excretion rates for all the modifications analyzed with respective r values for the lesions of (8-oxoGua) r = .891, p < .01; (8-oxodG) r = .998, p < .001; and (5-HMUra) r = .949, p < .005. However, only 8-oxoGua significantly correlates negatively with maximum life span (MLSP) (r = -.928, p < .01). Despite substantial differences in MLSP between humans and pigs (120 and 27 years, respectively), the rates of excretion of all measured modifications were very similar. The urinary levels of all measured modifications found in our study for mouse and humans account respectively for about 34,000 and 2800 repaired events per average cell, per 24 h. It is therefore possible that the high metabolic rate in mice (or other short-lived animals) may be responsible for severe everyday oxidative DNA insults that may be accumulated faster than in long-lived species.

Animals↗
PubMed2004

Diet is not responsible for the presence of several oxidatively damaged DNA lesions in mouse urine.

In order to eliminate the possibility that diet may influence urinary oxidative DNA lesion levels, in our experiments we used a recently developed technique involving HPLC pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection. This methodology was applied for the determination of the lesions: 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 5-(hydroxymethyl)uracil (5HMUra) in the urine of mice fed with nucleic acid free diet and normal, unrestricted diet. The mean levels of 8-oxoGua, 8-oxodGuo and 5HMUra of the animals fed the normal diet reached the mean values of 15.6 +/- 3.5, 2.0 +/- 0.53 and 16.8 +/- 10.4 nmol/kg/24 h, After feeding the mice for 12 days with nucleic acid free diet the respective values were 18.8 +/- 4.6, 1.6 +/- 0.3 and 25.4 +/- 10.5 nmol/kg/24 h, respectively. The results clearly demonstrate that irrespective of the diet, the excretion rates were not statistically different during the course of feeding. The respective p values for the differences between lesions in the two types of diets were: 0.13 (8-oxoGua), 0.16 (8-oxodGuo), 0.18 (5-HMUra). Our results clearly indicate that diet does not contribute to urinary excretion of the lesions in mouse model.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Oxidative DNA damage in cancer patients: a cause or a consequence of the disease development?

A wide variety of oxidative DNA lesions are present in living cells. One of the best known lesions of this type is 8-oxoguanine (8-oxoGua) which has been shown to have mutagenic properties. An influence of antioxidative vitamins and labile iron pool on the background level of 8-oxoGua in cellular DNA is discussed and oxidative damage to free nucleotide pool as a possible source of 8-oxo-2'-deoxyguanosine in DNA and urine is described. An involvement of 8-oxoGua in the origin and/or progression of cancer is reviewed. It is concluded that a severe oxidative stress manifested as a high level of 8-oxoGua in cellular DNA as well as in urine of cancer patients is a consequence of development of many types of cancer. Although at present it is impossible to answer directly the question concerning involvement of oxidative DNA damage in cancer etiology it is likely that oxidative DNA base modifications may serve as a source of mutations that initiate carcinogenesis (i.e. they may be causal factors responsible for the process).

Carcinogens↗
PubMed2003

Products of oxidative DNA damage and repair as possible biomarkers of susceptibility to lung cancer.

The broad spectrum of oxidative DNA damage biomarkers [urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OH-dGuo) and 8-hydroxyguanine (8-OH-Gua)] and the level of oxidative DNA damage and repair in leukocytes DNA were analyzed in three groups of subjects: (a) lung cancer patients [all smokers (n = 51)]; (b) healthy smokers with comparable smoking status (n = 26); and (c) healthy nonsmokers (n = 38). The mean level of 8-OH-Gua in urine samples of 38 healthy nonsmokers reached a value of 1.783 +/- 0.785 nmol/day/kg. This level was significantly lower than that in the urine of the two smoker groups (cancer patients and healthy smokers), in whom the levels reached values of 2.319 +/- 1.271 and 2.824 +/- 0.892 nmol/day/kg, respectively. Urinary excretion of 8-OH-dGuo was similar in all groups of subjects. The level of 8-OH-dGuo in DNA isolated from leukocytes of cancer patients was significantly higher than that in DNA isolated from the group of healthy smokers and nonsmokers (9.44 +/- 4.77 versus 7.20 +/- 2.83 and 5.88 +/- 2.47 molecules/10(6) deoxyguanosine, respectively). Repair activity of 8-OH-Gua, as estimated by the nicking assay, was significantly higher in blood leukocytes of healthy volunteers (44.6 +/- 20.21 and 37.54 +/- 13.43 pmol/h/mg protein for smokers and nonsmokers, respectively) than in the leukocytes of lung cancer patients (24.56 +/- 11.28 pmol/h/mg protein). Because oxidative DNA insult represented by urinary excretion of oxidative DNA lesions was similar in both groups of subjects with similar smoking status, it appears likely that a higher rate of generation of oxidative damage in cellular DNA of lung cancer patients is a result of deficiency of the repair mechanism(s) in this group.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Cellular level of 8-oxo-2'-deoxyguanosine in DNA does not correlate with urinary excretion of the modified base/nucleoside.

We assessed a relationship between the level of 8-oxodG in leukocyte DNA measured with the high performance liquid chromatography with electrochemical detection (HPLC/EC) technique and urinary excretion of the modified nucleoside/base analysed with a recently developed methodology involving HPLC prepurification followed by gas chromatography with isotope dilution mass spectrometric detection. No correlation was found between these markers of oxidative DNA damage commonly used in epidemiological studies. Several possible explanations of this finding are discussed.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Persistent oxidative stress in colorectal carcinoma patients.

We examine whether the level of 8-oxo-2'-deoxyguanosine (8-oxodGuo) in lymphocytes DNA is higher in colon cancer when compared to the control group. Factors that may influence oxidative stress such as antioxidant vitamins and uric acid were also determined. Blood samples were obtained from a control group of 55 healthy persons and 43 colon cancers. 8-OxodGuo level and the vitamins concentration were measured by high-performance liquid chromatography. The levels of 8-oxodGuo were significantly higher whereas the concentrations of the vitamins and uric acid were significantly lower in colon cancer patients than in control group. Therefore, the decreased concentration of antioxidant vitamins together with lower amount of uric acid may be responsible for the formation of pro-oxidative environment in blood of colorectal carcinoma patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome.

Free radical attack upon DNA generates a multiplicity of DNA damage, including modified bases. Some of these modifications have considerable potential to damage the integrity of the genome. This article reviews recent data that suggest the involvement of oxidative DNA damage in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome (AIDS). There is evidence that oxidative DNA damage may play a causative role in atherosclerosis. Oxidative DNA damage may lead to apoptotic cell death of patients infected with human immunodeficiency virus (HIV) and may influence the progression of AIDS. While many details regarding the role of reactive oxygen species-induced DNA damage in the etiology of complex multifactorial diseases like cancer are yet to be discovered, evidence suggests that oxidants act at several stages in the malignant transformation of cells. However, the quantitative relationship between the measured DNA damage and the development of cancer is still lacking.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients.

There is evidence suggesting that patients infected with human immunodeficiency virus (HIV) are under chronic oxidative stress. In the present study, the level of oxidatively modified bases in lymphocyte DNA and some other parameters of oxidative stress were measured in HIV-infected patients (n = 30), as well as in control groups (10 healthy volunteers and 15 HIV-seronegative injected drug users). Additional experiments were conducted using lymphocyte DNA samples from asymptomatic seropositive, HIV-infected patients who were supplemented with antioxidant vitamins A, C, and E or received placebo. Significant increases in the amount of the modified DNA bases were observed in HIV-infected patients when compared with the control group. The concentration of thiobarbituric acid reactive substances (TBARS) was higher and activities of antioxidant enzymes (superoxide dismutase and catalase) were lower in the group of HIV-infected patients in comparison to the control group. Vitamin supplementation resulted in the significant decrease in the levels of all modified DNA bases when compared to the patients who received placebo. The reduction of TBARS and the restoration of the activity of the enzymes were also observed. Our data suggest that people infected with HIV can benefit from treatment with antioxidant vitamins.

Adolescent↗