22 results on '"Duthie, S. J."'
Search Results
2. The teacher, the learner and the method
- Author
-
Duthie, S J, primary and Garden, A S, additional
- Published
- 2010
- Full Text
- View/download PDF
3. Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers
- Author
-
Basten, G P, primary, Duthie, S J, additional, Pirie, L, additional, Vaughan, N, additional, Hill, M H, additional, and Powers, H J, additional
- Published
- 2006
- Full Text
- View/download PDF
4. Increased uracil misincorporation in lymphocytes from folate-deficient rats
- Author
-
Duthie, S J, primary, Grant, G, additional, and Narayanan, S, additional
- Published
- 2000
- Full Text
- View/download PDF
5. Folic acid deficiency and cancer: mechanisms of DNA instability
- Author
-
Duthie, S. J, primary
- Published
- 1999
- Full Text
- View/download PDF
6. Cryopreserved versus freshly isolated lymphocytes in human biomonitoring: endogenous and induced DNA damage, antioxidant status and repair capability.
- Author
-
Duthie, S. J., Pirie, L., Jenkinson, A. McE., and Narayanan, S.
- Subjects
CRYOBIOLOGY ,CRYOPRESERVATION of organs, tissues, etc. ,HUMAN cell culture ,LYMPHOCYTES ,NUCLEIC acids ,DNA ,GENETIC mutation - Abstract
Lymphocytes are routinely used in human biomonitoring to assess the potential toxic and cytoprotective effects of diet on both DNA damage and repair and, by implication, health. Logistically, samples may require to be cryopreserved and stored. How this affects cells used in human biomonitoring is often not considered. In this study we have evaluated the influence of cryopreservation on endogenous and induced DNA strand breakage, altered bases (oxidized purines, oxidized pyrimidines and misincorporated uracil), antioxidant capacity and DNA repair capability in human peripheral blood lymphocytes. Neither isolation nor freezing increased DNA strand breakage above endogenous levels found in freshly isolated human lymphocytes. Oxidized bases (both pyrimidines and purines) and misincorporated uracil, were similar for fresh and frozen lymphocytes. Fresh and frozen lymphocytes responded almost identically to hydrogen peroxide. Quercetin-mediated cytoprotection against hydrogen peroxide-induced strand breakage was maintained in cryopreserved lymphocytes after short-term (24 h) and longer term (2 months) storage compared with freshly isolated and treated cells. Hydrogen peroxide-induced DNA strand breakage was repaired in fresh lymphocytes. Cryopreserved lymphocytes were unable to repair oxidant-induced DNA strand breaks. Frozen human lymphocytes can therefore be successfully used for most aspects of DNA damage biomonitoring, but not for repair. [ABSTRACT FROM PUBLISHER]
- Published
- 2002
- Full Text
- View/download PDF
7. Lysis of whole blood in vitro causes DNA strand breaks in human lymphocytes.
- Author
-
Narayanan, S., O'Donovan, M. R., and Duthie, S. J.
- Subjects
DNA damage ,LYMPHOCYTES ,GEL electrophoresis ,ERYTHROCYTES ,BLOOD testing - Abstract
DNA damage in lymphocytes, as measured by alkaline single cell gel electrophoresis (pH 12.7), is greatly increased by the concurrent lysis of whole blood in both freshly isolated samples and in PHA-stimulated cultures over a period of 7 days. Further, there is a marked progressive increase in DNA damage with time in PHA-stimulated lymphocytes cultured in whole blood even when the lymphocytes are separated before analysis; no such increase is seen in lymphocytes cultured alone. This indicates that there are components in whole blood that can cause DNA damage in lymphocytes, with granulocytes and lysis of red blood cells likely candidates. The DNA damage is greatly reduced in granulocyte-depleted whole blood cultures, but even in these significant increases are seen at later sampling times. Consequently, careful sample preparation is of paramount importance if the Comet assay is to be successfully used to assess DNA damage in human peripheral blood lymphocytes. Further, the progressive increase in DNA damage in whole blood cultures may influence other methods using lymphocytes for population biomonitoring and may be significant for in vitro genotoxicity testing. [ABSTRACT FROM PUBLISHER]
- Published
- 2001
- Full Text
- View/download PDF
8. Uracil misincorporation in human DNA detected using single cell gel electrophoresis.
- Author
-
Duthie, S J and McMillan, P
- Abstract
Poor folate status may be important in the aetiology of several epithelial cell malignancies including cancer of the uterine cervix. Folic acid is essential in the synthesis of purine nucleotides and the pyrimidine nucleoside thymidine and it is probable that imbalances in these DNA precursors negatively effect DNA stability and may ultimately lead to malignant transformation. The development of a modified 'comet assay' using the bacterial DNA repair enzyme uracil DNA glycosylase, to detect misincorporated uracil in human DNA is reported here. The effect of perturbing folic acid and deoxyuridine levels on uracil misincorporation in normal human lymphocytes and cultured human tumour cells was investigated using this assay. HeLa cells and peripheral human lymphocytes incubated as agarose-embedded nucleoids, with 1 unit of uracil DNA glycosylase per microg of DNA, contained low levels of uracil in their DNA. Both HeLa cells and stimulated human lymphocytes cultured in folate-deficient medium were growth arrested. Incubating human lymphocytes in folate-deficient medium significantly increased the level of uracil detected compared with control cells. HeLa cells showed an increase in non-specific DNA damage (strand breaks). Deoxyuridine (100 microM) significantly increased the level of uracil detected in the DNA of both folate-deficient and control HeLa cells. It appears that this modified comet assay specifically detects misincorporated uracil in single human cells. It should, therefore, prove valuable in determining the role of folic acid status in DNA instability and cancer. [ABSTRACT FROM PUBLISHER]
- Published
- 1997
- Full Text
- View/download PDF
9. Serum carotenoids and oxidative DNA damage in human lymphocytes.
- Author
-
Collins, A R, Olmedilla, B, Southon, S, Granado, F, and Duthie, S J
- Abstract
Carotenoids are thought to act as antioxidants in vivo, decreasing oxidative damage to biomolecules and thus protecting against coronary heart disease and cancer. However, human intervention studies with beta-carotene have given equivocal results in terms of cancer incidence. In an alternative molecular epidemiological approach, we have employed the 'comet assay' (single cell alkaline gel electrophoresis) to measure strand breaks, oxidized pyrimidines and altered purines in the DNA of lymphocytes from volunteers supplemented with alpha/beta-carotene, lutein, lycopene or placebo. In addition, we measured concentrations of the main serum carotenoids, and vitamins E and C, by HPLC. We report a significant negative correlation between basal concentrations of total serum carotenoids and oxidized pyrimidines. A similar correlation was seen between individual carotenoids (notably lutein and beta-carotene) and oxidized pyrimidines. However, carotenoid supplementation did not have a significant effect on endogenous oxidative damage. This suggests that there are some factors in the basal diet, probably found in fruit and vegetables, that decrease oxidative damage to DNA. In this case, basal serum carotenoids may simply be markers of consumption of fruit and vegetables, they themselves having little or no protective value.
- Published
- 1998
- Full Text
- View/download PDF
10. Morbidity after termination of pregnancy in first trimester.
- Author
-
Duthie, S J, Hobson, D, Tait, I A, Pratt, B C, Lowe, N, Sequeira, P J, and Hargreaves, C
- Abstract
The outcome of termination of pregnancy was observed in relation to the preoperative clinical and microbiological findings in 167 women attending a day care abortion unit in Liverpool. Before termination, Chlamydia trachomatis was isolated from the cervix of 19 (11%) of the patients and high counts (greater than 10(4) colour changing units (ccu) per ml of specimen) of mycoplasmas were found in 30 (18%). Coexistent infections with chlamydiae and high counts of mycoplasmas occurred in only seven (4%) women. Trichomonas vaginalis, yeasts, or pathogenic bacteria were found in vaginal swabs from 30 (18%) women. After undergoing termination, seven (4%) women developed pelvic inflammatory disease (PID), five (71%) of whom had yielded C trachomatis before undergoing termination. A further 13 (8%) patients developed minor morbidity of the upper genital tract; high count mycoplasmal infection had been found in seven (54%) and chlamydial infection in three (23%) of these women before termination. In contrast, C trachomatis had been isolated from only 11 (8%) and high counts of mycoplasmas from 23 (16%) of the 147 women who had uneventful recoveries after undergoing termination. No correlation was apparent between the presence of vaginal pathogens before termination and the development of untoward sequelae postoperatively. Neither the history nor clinical examination before termination would have indicated that chlamydial or mycoplasmal infections were present, or that postoperative complications were likely to occur. Abnormal cervical cytology, however, was found in 86 (52%) of women overall, including 15 (79%) of the 19 women with chlamydial infection. [ABSTRACT FROM PUBLISHER]
- Published
- 1987
- Full Text
- View/download PDF
11. Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism.
- Author
-
Elliott, R. M. (R. M.), de Roos, B. (B.), Duthie, S. J. (S. J.), Bouwman, F. G. (F. G.), Rubio-Aliaga, I. (I.), Crosley, L. K. (L. K.), Mayer, C. (C.), Polley, A. C. (A. C.), Heim, C. (C.), Coort, S. L. (S. L.), Evelo, C. T. (C. T.), Mulholland, F. (F.), Daniel, H. (H.), Mariman, E. C. (E. C.), Johnson, I. T. (I. T.), Elliott, R. M. (R. M.), de Roos, B. (B.), Duthie, S. J. (S. J.), Bouwman, F. G. (F. G.), Rubio-Aliaga, I. (I.), Crosley, L. K. (L. K.), Mayer, C. (C.), Polley, A. C. (A. C.), Heim, C. (C.), Coort, S. L. (S. L.), Evelo, C. T. (C. T.), Mulholland, F. (F.), Daniel, H. (H.), Mariman, E. C. (E. C.), and Johnson, I. T. (I. T.)
- Abstract
There is growing interest in the potential health benefits of diets that involve regular periods of fasting. While animal studies have provided compelling evidence that feeding patterns such as alternate-day fasting can increase longevity and reduce incidence of many chronic diseases, the evidence from human studies is much more limited and equivocal. Additionally, although several candidate processes have been proposed to contribute to the health benefits observed in animals, the precise molecular mechanisms responsible remain to be elucidated. The study described here examined the effects of an extended fast on gene transcript profiles in peripheral blood mononuclear cells from ten apparently healthy subjects, comparing transcript profiles after an overnight fast, sampled on four occasions at weekly intervals, with those observed on a single occasion after a further 24 h of fasting. Analysis of the overnight fasted data revealed marked inter-individual differences, some of which were associated with parameters such as gender and subject body mass. For example, a striking positive association between body mass index and the expression of genes regulated by type 1 interferon was observed. Relatively subtle changes were observed following the extended fast. Nonetheless, the pattern of changes was consistent with stimulation of fatty acid oxidation, alterations in cell cycling and apoptosis and decreased expression of key pro-inflammatory genes. Stimulation of fatty acid oxidation is an expected response, most likely in all tissues, to fasting. The other processes highlighted provide indications of potential mechanisms that could contribute to the putative beneficial effects of intermittent fasting in humans.
12. Folate, genomic stability and colon cancer: the use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring.
- Author
-
Catala, G. N. (Gema Nadal), Bestwick, C. S. (Charles S.), Russell, W. R. (Wendy R.), Tortora, K. (Katia), Giovannelli, L. (Lisa), Moyer, M. P. (Mary Pat), Lendoiro, E. (Elena), Duthie, S. J. (Susan J.), Catala, G. N. (Gema Nadal), Bestwick, C. S. (Charles S.), Russell, W. R. (Wendy R.), Tortora, K. (Katia), Giovannelli, L. (Lisa), Moyer, M. P. (Mary Pat), Lendoiro, E. (Elena), and Duthie, S. J. (Susan J.)
- Abstract
Intake of folate (vitamin B9) is strongly inversely linked with human cancer risk, particularly colon cancer. In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing colon cancer. Folate acts in normal cellular metabolism to maintain genomic stability through the provision of nucleotides for DNA replication and DNA repair and by regulating DNA methylation and gene expression. Folate deficiency can accelerate carcinogenesis by inducing misincorporation of uracil into DNA, by increasing DNA strand breakage, by inhibiting DNA base excision repair capacity and by inducing DNA hypomethylation and consequently aberrant gene and protein expression. Conversely, increasing folate intake may improve genomic stability. This review describes key applications of single cell gel electrophoresis (the comet assay) in assessing genomic instability (misincorporated uracil, DNA single strand breakage and DNA repair capacity) in response to folate status (deficient or supplemented) in human cells in vitro, in rodent models and in human case-control and intervention studies. It highlights an adaptation of the SCGE comet assay for measuring genome-wide and gene-specific DNA methylation in human cells and colon tissue.
13. Roadmap for investigating epigenome deregulation and environmental origins of cancer.
- Author
-
Herceg, Z. (Zdenko), Ghantous, A. (Akram), Wild, C. P. (Christopher P.), Sklias, A. (Athena), Casati, L. (Lavinia), Duthie, S. J. (Susan J.), Fry, R. (Rebecca), Issa, J. (Jean‐Pierre), Kellermayer, R. (Richard), Koturbash, I. (Igor), Kondo, Y. (Yukata), Lepeule, J. (Johanna), Lima, S. C.S. (Sheila C.S.), Marsit, C. J. (Carmen J.), Rakyan, V. (Vardhman), Saffery, R. (Richard), Taylor, J. A. (Jack A.), Teschendorff, A. E. (Andrew E.), Ushijima, T. (Toshikazu), Vineis, P. (Paolo), Walker, C. L. (Cheryl Lyn), Waterland, R. A. (Robert A.), Wiemels, J. (Joe), Ambatipudi, S. (Srikant), Esposti, D. D. (Davide Degli), Hernandez‐Vargas, H. (Hector), Herceg, Z. (Zdenko), Ghantous, A. (Akram), Wild, C. P. (Christopher P.), Sklias, A. (Athena), Casati, L. (Lavinia), Duthie, S. J. (Susan J.), Fry, R. (Rebecca), Issa, J. (Jean‐Pierre), Kellermayer, R. (Richard), Koturbash, I. (Igor), Kondo, Y. (Yukata), Lepeule, J. (Johanna), Lima, S. C.S. (Sheila C.S.), Marsit, C. J. (Carmen J.), Rakyan, V. (Vardhman), Saffery, R. (Richard), Taylor, J. A. (Jack A.), Teschendorff, A. E. (Andrew E.), Ushijima, T. (Toshikazu), Vineis, P. (Paolo), Walker, C. L. (Cheryl Lyn), Waterland, R. A. (Robert A.), Wiemels, J. (Joe), Ambatipudi, S. (Srikant), Esposti, D. D. (Davide Degli), and Hernandez‐Vargas, H. (Hector)
- Abstract
The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor-specific ('fingerprints') that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed as well as advances in epigenomics that may help an understanding of the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed as well as how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment.
14. Roadmap for investigating epigenome deregulation and environmental origins of cancer.
- Author
-
Herceg, Z. (Zdenko), Ghantous, A. (Akram), Wild, C. P. (Christopher P.), Sklias, A. (Athena), Casati, L. (Lavinia), Duthie, S. J. (Susan J.), Fry, R. (Rebecca), Issa, J. (Jean?Pierre), Kellermayer, R. (Richard), Koturbash, I. (Igor), Kondo, Y. (Yukata), Lepeule, J. (Johanna), Lima, S. C.S. (Sheila C.S.), Marsit, C. J. (Carmen J.), Rakyan, V. (Vardhman), Saffery, R. (Richard), Taylor, J. A. (Jack A.), Teschendorff, A. E. (Andrew E.), Ushijima, T. (Toshikazu), Vineis, P. (Paolo), Walker, C. L. (Cheryl Lyn), Waterland, R. A. (Robert A.), Wiemels, J. (Joe), Ambatipudi, S. (Srikant), Esposti, D. D. (Davide Degli), Hernandez?Vargas, H. (Hector), Herceg, Z. (Zdenko), Ghantous, A. (Akram), Wild, C. P. (Christopher P.), Sklias, A. (Athena), Casati, L. (Lavinia), Duthie, S. J. (Susan J.), Fry, R. (Rebecca), Issa, J. (Jean?Pierre), Kellermayer, R. (Richard), Koturbash, I. (Igor), Kondo, Y. (Yukata), Lepeule, J. (Johanna), Lima, S. C.S. (Sheila C.S.), Marsit, C. J. (Carmen J.), Rakyan, V. (Vardhman), Saffery, R. (Richard), Taylor, J. A. (Jack A.), Teschendorff, A. E. (Andrew E.), Ushijima, T. (Toshikazu), Vineis, P. (Paolo), Walker, C. L. (Cheryl Lyn), Waterland, R. A. (Robert A.), Wiemels, J. (Joe), Ambatipudi, S. (Srikant), Esposti, D. D. (Davide Degli), and Hernandez?Vargas, H. (Hector)
- Abstract
The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor-specific ('fingerprints') that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed as well as advances in epigenomics that may help an understanding of the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed as well as how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment.
15. Folate, genomic stability and colon cancer: the use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring.
- Author
-
Catala, G. N. (Gema Nadal), Bestwick, C. S. (Charles S.), Russell, W. R. (Wendy R.), Tortora, K. (Katia), Giovannelli, L. (Lisa), Moyer, M. P. (Mary Pat), Lendoiro, E. (Elena), Duthie, S. J. (Susan J.), Catala, G. N. (Gema Nadal), Bestwick, C. S. (Charles S.), Russell, W. R. (Wendy R.), Tortora, K. (Katia), Giovannelli, L. (Lisa), Moyer, M. P. (Mary Pat), Lendoiro, E. (Elena), and Duthie, S. J. (Susan J.)
- Abstract
Intake of folate (vitamin B9) is strongly inversely linked with human cancer risk, particularly colon cancer. In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing colon cancer. Folate acts in normal cellular metabolism to maintain genomic stability through the provision of nucleotides for DNA replication and DNA repair and by regulating DNA methylation and gene expression. Folate deficiency can accelerate carcinogenesis by inducing misincorporation of uracil into DNA, by increasing DNA strand breakage, by inhibiting DNA base excision repair capacity and by inducing DNA hypomethylation and consequently aberrant gene and protein expression. Conversely, increasing folate intake may improve genomic stability. This review describes key applications of single cell gel electrophoresis (the comet assay) in assessing genomic instability (misincorporated uracil, DNA single strand breakage and DNA repair capacity) in response to folate status (deficient or supplemented) in human cells in vitro, in rodent models and in human case-control and intervention studies. It highlights an adaptation of the SCGE comet assay for measuring genome-wide and gene-specific DNA methylation in human cells and colon tissue.
16. Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism.
- Author
-
Elliott, R. M. (R. M.), de Roos, B. (B.), Duthie, S. J. (S. J.), Bouwman, F. G. (F. G.), Rubio-Aliaga, I. (I.), Crosley, L. K. (L. K.), Mayer, C. (C.), Polley, A. C. (A. C.), Heim, C. (C.), Coort, S. L. (S. L.), Evelo, C. T. (C. T.), Mulholland, F. (F.), Daniel, H. (H.), Mariman, E. C. (E. C.), Johnson, I. T. (I. T.), Elliott, R. M. (R. M.), de Roos, B. (B.), Duthie, S. J. (S. J.), Bouwman, F. G. (F. G.), Rubio-Aliaga, I. (I.), Crosley, L. K. (L. K.), Mayer, C. (C.), Polley, A. C. (A. C.), Heim, C. (C.), Coort, S. L. (S. L.), Evelo, C. T. (C. T.), Mulholland, F. (F.), Daniel, H. (H.), Mariman, E. C. (E. C.), and Johnson, I. T. (I. T.)
- Abstract
There is growing interest in the potential health benefits of diets that involve regular periods of fasting. While animal studies have provided compelling evidence that feeding patterns such as alternate-day fasting can increase longevity and reduce incidence of many chronic diseases, the evidence from human studies is much more limited and equivocal. Additionally, although several candidate processes have been proposed to contribute to the health benefits observed in animals, the precise molecular mechanisms responsible remain to be elucidated. The study described here examined the effects of an extended fast on gene transcript profiles in peripheral blood mononuclear cells from ten apparently healthy subjects, comparing transcript profiles after an overnight fast, sampled on four occasions at weekly intervals, with those observed on a single occasion after a further 24 h of fasting. Analysis of the overnight fasted data revealed marked inter-individual differences, some of which were associated with parameters such as gender and subject body mass. For example, a striking positive association between body mass index and the expression of genes regulated by type 1 interferon was observed. Relatively subtle changes were observed following the extended fast. Nonetheless, the pattern of changes was consistent with stimulation of fatty acid oxidation, alterations in cell cycling and apoptosis and decreased expression of key pro-inflammatory genes. Stimulation of fatty acid oxidation is an expected response, most likely in all tissues, to fasting. The other processes highlighted provide indications of potential mechanisms that could contribute to the putative beneficial effects of intermittent fasting in humans.
17. Sexually transmitted diseases amongst pregnant Vietnamese refugees in Hong Kong.
- Author
-
King, P A, Duthie, S J, and Ma, H K
- Abstract
In a prospective study the prevalence of syphilis amongst a group of pregnant Vietnamese refugees in Hong Kong was found to be 3.4%. No cases of gonorrhoea, genital warts or genital ulcers were found in the same group of patients. The implications of these results are discussed and the importance of adequate screening, treatment, contact tracing and health education amongst this group are emphasised. [ABSTRACT FROM PUBLISHER]
- Published
- 1990
- Full Text
- View/download PDF
18. Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study.
- Author
-
Boyle SP, Dobson VL, Duthie SJ, Hinselwood DC, Kyle JA, and Collins AR
- Subjects
- Absorption, Adolescent, Adult, Biological Availability, DNA Damage, Female, Flavonoids metabolism, Humans, Liver physiology, Middle Aged, Nutritional Status, Phenol blood, Seasons, Single-Blind Method, Time Factors, Antioxidants administration & dosage, Antioxidants pharmacokinetics, Flavonoids blood, Oxidative Stress drug effects, Rutin administration & dosage, Rutin pharmacokinetics
- Abstract
Objective: To determine the potential antioxidant effect of rutin (quercetin-3-O-beta-rutinoside) supplementation., Design: A 6-week randomized single-blind placebo controlled trial was conducted; 500 mg rutin supplement was compared to an equivalent amount of glucose placebo. In addition, a pharmacokinetic study was carried out., Setting: The Rowett Research Institute, Aberdeen, UK., Subjects: Eighteen healthy non-obese normocholesterolaemic female volunteers in the age range 18-48 y., Main Outcome Measures: Plasma flavonoids, ascorbic acid, tocopherols and carotenoids, plasma antioxidant capacity, lymphocyte DNA damage, blood chemistry and haematology, liver function tests, urinary malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-iso-prostaglandin F2alpha., Results: Eighteen volunteers completed the trial. Rutin supplementation did not induce any adverse changes in blood chemistry or indices of liver function. Plasma flavonoids were significantly elevated in the rutin-supplemented group. Endogenous oxidation of pyrimidines was significantly decreased in both rutin- and placebo-treated volunteers. There was no significant change in the level of urinary 8-hydroxy-2'-deoxyguanosine or urinary malondialdehyde in either group. A linear correlation was observed between urinary malondialdehyde and urinary 8-iso-prostaglandin F2alpha (R = 0.54, P<0.01)., Conclusion: Six weeks' rutin supplementation significantly elevated the levels of three plasma flavonoids (quercetin. kaempferol and isorhamnetin) but there was no significant change in plasma antioxidant status. The decrease in the level of endogenous base oxidation in lymphocyte DNA seen in both the placebo- and rutin-supplemented subjects may reflect seasonal changes in other dietary antioxidants.
- Published
- 2000
- Full Text
- View/download PDF
19. Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants.
- Author
-
Duthie GG, Duthie SJ, and Kyle JA
- Abstract
Certain dietary antioxidants such as vitamin E and vitamin C are important for maintaining optimum health. There is now much interest in polyphenolic products of the plant phenylpropanoid pathway as they have considerable antioxidant activity in vitro and are ubiquitous in our diet. Rich sources include tea, wine, fruits and vegetables although levels are affected by species, light, degree of ripeness, processing and storage. This confounds the formulation of databases for the estimation of dietary intakes. Most attention to date has focused on the flavonoids, a generic term which includes chalcones, flavones, flavanones, flavanols and anthocyanins. There is little convincing epidemiological evidence that intakes of polyphenols are inversely related to the incidence of cancer whereas a number of studies suggest that high intakes of flavonoids may be protective against CHD. In contrast, numerous cell culture and animal models indicate potent anticarcinogenic activity by certain polyphenols mediated through a range of mechanisms including antioxidant activity, enzyme modulation, gene expression, apoptosis, upregulation of gap junction communication and P-glycoprotein activation. Possible protective effects against heart disease may be due to the ability of some polyphenols to prevent the oxidation of LDL to an atherogenic form although anti-platelet aggregation activity and vasodilatory properties are also reported. However, some polyphenols are toxic in mammalian cells. Thus, until more is known about their bioavailability, metabolism and intracellular location, increasing intakes of polyphenols by supplements or food fortification may be unwise.
- Published
- 2000
- Full Text
- View/download PDF
20. Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes.
- Author
-
Duthie SJ, Ma A, Ross MA, and Collins AR
- Subjects
- Biotransformation, Double-Blind Method, Humans, Hydrogen Peroxide toxicity, Lymphocytes metabolism, Male, Middle Aged, Oxidation-Reduction, Smoking blood, Antioxidants administration & dosage, DNA drug effects, DNA Damage, Lymphocytes drug effects
- Abstract
The association between high intake of fruit and vegetables and low incidence of certain cancers is well established. Dietary antioxidants present in these foods are thought to decrease free radical attack on DNA and hence to protect against mutations that cause cancer, but this causal mechanism remains conjectural. We have adopted a molecular epidemiological approach to this question, based on a modified alkaline single-cell gel electrophoresis assay ("comet assay") which specifically detects oxidation of pyrimidines in the DNA of human lymphocytes. In a survey of men 50-59 years of age living in the northeast of Scotland, smokers initially showed significantly more base damage than nonsmokers. Correlations between oxidative base damage and plasma concentrations of various antioxidants were generally negative but not statistically significant. Supplementation of the diet for 20 weeks with vitamin C (100 mg/day), vitamin E (280 mg/day), and beta-carotene (25 mg/day) resulted in a highly significant (P < 0.002) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmokers. In addition, lymphocytes of antioxidant-supplemented subjects showed an increased resistance to oxidative damage when challenged in vitro with H2O2. These findings strongly support the hypothesis that fruit and vegetables exert a cancer-protective effect via a decrease in oxidative damage to DNA.
- Published
- 1996
21. The role of reductive and oxidative metabolism in the toxicity of mitoxantrone, adriamycin and menadione in human liver derived Hep G2 hepatoma cells.
- Author
-
Duthie SJ and Grant MH
- Subjects
- Carcinoma, Hepatocellular metabolism, Humans, Liver Neoplasms metabolism, Oxidation-Reduction, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured metabolism, Carcinoma, Hepatocellular drug therapy, Doxorubicin therapeutic use, Liver Neoplasms drug therapy, Mitoxantrone therapeutic use, Vitamin K therapeutic use
- Abstract
The cytotoxic properties of quinones, such as menadione, are mediated through one electron reduction to yield semi-quinone radicals which can subsequently enter redox cycles with molecular oxygen leading to the formation of reactive oxygen radicals. In this study the role of reduction and oxidation in the toxicity of mitoxantrone was studied and its toxicity compared with that of adriamycin and menadione. The acute toxicity of mitoxantrone was not mediated through one-electron reduction, since inhibition of the enzymes glutathione reductase and catalase, responsible for protecting the cells against oxidative damage, did not affect its toxicity. Adriamycin was the most potent inhibitor of protein and RNA synthesis of the three quinones. Menadione, at concentrations up to 25 microM, did not inhibit either protein or RNA synthesis unless dicoumarol, an inhibitor of DT-diaphorase, was also present. The two-electron reduction of menadione by DT-diaphorase is therefore a protective mechanism in the cell. This enzyme also protected against the toxicity of high concentrations (100 microM) of mitoxantrone. The inhibitory effect of mitoxantrone, but not of menadione or adriamycin, on cell growth was prevented by inhibiting the activity of cytochrome P450-dependent mixed function oxidase (MFO) system using metyrapone. This suggests that mitoxantrone is oxidised to a toxic intermediate by the MFO system.
- Published
- 1989
- Full Text
- View/download PDF
22. The influence of culture medium composition on drug metabolising enzyme activities of the human liver derived Hep G2 cell line.
- Author
-
Doostdar H, Duthie SJ, Burke MD, Melvin WT, and Grant MH
- Subjects
- Cell Line, Culture Media, Glutathione metabolism, Humans, Kinetics, Carcinoma, Hepatocellular enzymology, Cytochrome P-450 Enzyme System metabolism, Glucuronosyltransferase metabolism, Glutathione Transferase metabolism, Liver Neoplasms enzymology, Mixed Function Oxygenases metabolism
- Abstract
When grown in the standard Dulbecco's medium the human liver derived Hep G2 hepatoma cell line shows only 10-20% of the cytochrome P-450-dependent mixed function oxidase (MFO) activity of freshly isolated human adult hepatocytes. However, the MFO activities and, to a lesser extent, the activities of UDP-glucuronyltransferase and glutathione-S-transferase can be increased by altering the composition of the growth medium. Modified Earle's medium was more effective in this respect than Williams' E medium and increased the O-dealkylations of ethoxyresorufin, benzyloxyresorufin and pentoxyresorufin 50-, 30- and 10-fold, respectively.
- Published
- 1988
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.