Displaying publications 41 - 53 of 53 in total

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  1. Reduction of DNA damage in older healthy adults by Tri E Tocotrienol supplementation
    Chin SF, Hamid NA, Latiff AA, Zakaria Z, Mazlan M, Yusof YA, et al.
    Nutrition, 2008 Jan;24(1):1-10.
    PMID: 17884341
    The free radical theory of aging (FRTA) suggests that free radicals are the leading cause of deteriorating physiologic function during senescence. Free radicals attack cellular structures or molecules such as DNA resulting in various modifications to the DNA structures. Accumulation of unrepaired DNA contributes to a variety of disorders associated with the aging process.
    Matched MeSH terms: Comet Assay
  2. Contribution of CYP2E1 polymorphism to aging in the mechanical workshop workers
    Eshkoor SA, Ismail P, Rahman SA, Adon MY, Devan RV
    Toxicol. Mech. Methods, 2013 May;23(4):217-22.
    PMID: 23193996 DOI: 10.3109/15376516.2012.743637
    Aging is attributed to both genetic and environmental factors. Occupational exposure is one of the environmental factors with potential genotoxic effects. Researchers try to determine factors involved in genetic damages at hazards exposure that could accelerate aging. Cytochrome P450 2E1 (CYP2E1) gene contributes in activation and detoxification of the environmental hazards. This polymorphism plays an important role in susceptibility of inter-individuals to DNA damage at the occupational exposure. The current study evaluated the possible influence of this gene polymorphism in aging by genomic damages through the biomarkers alterations of micronuclei (MN), comet tail length and telomere length shortening at the exposure. In this study, buccal cells were collected from the oral cavity of exposed workers and non-exposed controls. The CYP2E1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The wild genotype significantly affected MN frequency (p = 0.007) and relative telomere length (p = 0.047) in the older group of workers. It was concluded that the interaction of gene polymorphism and exposure enhances DNA damage and accelerates aging consequently.
    Matched MeSH terms: Comet Assay
  3. Strobilanthes crispus Juice Concentrations and Anticancer Effects on DNA Damage, Apoptosis and Gene Expression in Hepatocellular Carcinoma Cells
    Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A, Eshak Z
    Asian Pac J Cancer Prev, 2015;16(14):6047-53.
    PMID: 26320494
    BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability.

    OBJECTIVE: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells.

    MATERIALS AND METHODS: MTT assays, flow cytometry, comet assays and the reverse transcription- polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers.

    RESULTS: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent.

    CONCLUSIONS: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

    Matched MeSH terms: Comet Assay
  4. A preliminary study of the effects of an extract of Ligularia fischeri leaves on type II collagen-induced arthritis in DBA/1J mice
    Choi EM, Kim YH
    Food Chem Toxicol, 2008 Jan;46(1):375-9.
    PMID: 17904263 DOI: 10.1016/j.fct.2007.08.018
    The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.
    Matched MeSH terms: Comet Assay
  5. Toxicological evaluation of some Malaysian locally processed raw food products
    Sharif R, Ghazali AR, Rajab NF, Haron H, Osman F
    Food Chem Toxicol, 2008 Jan;46(1):368-74.
    PMID: 17900779
    Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, p<0.05). To detect DNA damage in a single cell, alkaline Comet Assay was used. None of the extracts caused DNA damage to the Chang liver cells at 62.5 microg/ml following 24 h incubation, as compared to the positive control, hydrogen peroxide (tail moment - 9.50+/-1.50; tail intensity - 30.50+/-2.50). Proximate analysis which was used for the evaluation of macronutrients in food showed that shrimp paste did not comply with the protein requirement (<25%) as in Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.
    Matched MeSH terms: Comet Assay
  6. DNA damage and adduct formation in immune organs of developing chicks by polycyclic aromatic hydrocarbons
    Nisha AR, Hazilawati H, Mohd Azmi ML, Noordin MM
    Toxicol. Mech. Methods, 2017 Mar;27(3):215-222.
    PMID: 28030985 DOI: 10.1080/15376516.2016.1273432
    Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants and chemically a class of structurally similar chemical compounds characterized by the presence of fused aromatic rings. This research was undertaken to find out immunotoxic effects produced by pyrene, phenanthrene and fluoranthene. These chemicals were injected into developing chicks at three dose levels (0.2, 2 and 20 mg per kg) through allantioc route to rule out possible mechanisms involved in immunotoxicity. DNA adduct produced by PAHs in immune organs were analyzed by DNA adduct enzyme-linked immunosorbent assay (ELISA) kit and DNA damage was assessed by comet assay. A significant increase in the DNA adduct levels was found in thymus and bursa in 2 mg and 20 mg dose levels of pyrene, fluoranthene and phenanthrene treated groups, whereas those in spleen simulated the value of controls. Comet assay indicated that PAHs especially pyrene, fluoranthene and phenanthrene were capable of inducing increased level of comet parameters in thymus at all the dose levels. Bursa of Fabricius and spleen also showed a gradual rise in comet parameters corresponding to all dose levels, but the increase was more marked as in thymus. Thus, it can be concluded that DNA adducts produced by PAHs lead to single-strand breaks and reduced DNA repair, which ultimately begin a carcinogenic process. Hence, this experiment can be considered as a strong evidence of genotoxic potential of PAHs like pyrene, phenanthrene and fluoranthene in developing chicks.
    Matched MeSH terms: Comet Assay
  7. Comparing palm oil tocotrienol rich fraction with α-tocopherol supplementation on oxidative stress in healthy older adults
    Goon JA, Nor Azman NHE, Abdul Ghani SM, Hamid Z, Wan Ngah WZ
    Clin Nutr ESPEN, 2017 10;21:1-12.
    PMID: 30014863 DOI: 10.1016/j.clnesp.2017.07.004
    Vitamin E is a fat-soluble compound and powerful antioxidant that have been shown to protect the cell membranes against damage caused by free radicals. Human vitamin E supplementation studies are usually limited to α-tocopherol but currently tocotrienols are also available. This study aims to compare the effects of tocotrienol rich fraction (TRF) with α-tocopherol (α-TF) supplementation on oxidative stress in healthy male and female older adults aged 50-55 years old. A total of 71 subjects both male and female aged between 50 and 55 years were divided into groups receiving placebo (n = 23), α-TF (n = 24) and TRF (n = 24) for six months. Blood was taken at baseline (month 0), 3 months and 6 months osf supplementation for determination of plasma malondialdehyde (MDA), protein carbonyl, total DNA damage, vitamin D concentration and vitamin E isomers. α-TF supplementation reduced plasma MDA and protein carbonyl in female subjects after 3 and 6 months. TRF supplementation reduced MDA levels in both males and females as early as 3 months while DNA damage was reduced in females only at 6 months. Supplementation with α-TF and TRF increased plasma vitamin D concentration in both males and females after 6 months, but vitamin D concentration in male subjects were significantly higher compared to female subjects in TRF group. Vitamin E isomer determination showed α-TF, α-tocotrienol and γ-tocotrienol were increased in both male and female subjects. In conclusion, TRF supplementation effects were different from α-TF in reducing oxidative stress markers and vitamin D levels with a more pronounced effect in female subjects.
    Matched MeSH terms: Comet Assay
  8. Genotoxicity assessment of biphasic calcium phosphate of modified porosity on human dental pulp cells using Ames and Comet assays
    Wahab NFAC, Kannan TP, Mahmood Z, Rahman IA, Ismail H
    Toxicol In Vitro, 2018 Mar;47:207-212.
    PMID: 29247761 DOI: 10.1016/j.tiv.2017.12.002
    Biphasic Calcium Phosphate (BCP) with a ratio of 20/80 Hydroxyapatite (HA)/Beta-tricalcium phosphate (β-TCP) promotes the differentiation of human dental pulp cells (HDPCs). In the current study, the genotoxicity of locally produced BCP of modified porosity (65%) with a mean pore size of 300micrometer (μm) was assessed using Comet and Ames assays. HDPCs were treated with BCP extract at three different inhibitory concentrations which were obtained based on cytotoxicity test conducted with concurrent negative and positive controls. The tail moment of HDPCs treated with BCP extract at all three concentrations showed no significant difference compared to negative control (p>0.05), indicating that BCP did not induce DNA damage to HDPCs. The BCP was evaluated using five tester strains of Salmonella typhimurium TA98, TA100, TA102, TA1537 and TA1538. Each strain was incubated with BCP extract with five different concentrations in the presence and absence of metabolic activation system (S9) mix. Concurrently, negative and positive controls were included. The average number of revertant colonies per plate treated with the BCP extract was less than double as compared to the number of revertant colonies in negative control plate and no dose-related increase was observed. Results from both assays suggested that the BCP of modified porosity did not exhibit any genotoxic effect under the present test conditions.
    Matched MeSH terms: Comet Assay
  9. Zinc supplementation influences genomic stability biomarkers, antioxidant activity, and zinc transporter genes in an elderly Australian population with low zinc status
    Sharif R, Thomas P, Zalewski P, Fenech M
    Mol Nutr Food Res, 2015 Jun;59(6):1200-12.
    PMID: 25755079 DOI: 10.1002/mnfr.201400784
    An increased intake of Zinc (Zn) may reduce the risk of degenerative diseases but may prove to be toxic if taken in excess. This study aimed to investigate whether zinc carnosine supplement can improve Zn status, genome stability events, and Zn transporter gene expression in an elderly (65-85 years) South Australian cohort with low plasma Zn levels.
    Matched MeSH terms: Comet Assay
  10. Fulltext Goniothalamin-induced oxidative stress, DNA damage and apoptosis via caspase-2 independent and Bcl-2 independent pathways in Jurkat T-cells
    Inayat-Hussain SH, Chan KM, Rajab NF, Din LB, Chow SC, Kizilors A, et al.
    Toxicol Lett, 2010 Mar 1;193(1):108-14.
    PMID: 20026395 DOI: 10.1016/j.toxlet.2009.12.010
    Goniothalamin (GTN) isolated from Goniothalamus sp. has been demonstrated to induce apoptosis in a variety of cancer cell lines including Jurkat T leukemia cells. However, the mechanism of GTN-induced apoptosis upstream of mitochondria is still poorly defined. In this study, GTN caused a decrease in GSH with an elevation of reactive oxygen species as early as 30 min and DNA damage as assessed by Comet assay. Analysis using topoisomerase II processing of supercoiled pBR 322 DNA showed that GTN caused DNA damage via a topoisomerase II-independent pathway suggesting that cellular oxidative stress may contribute to genotoxicity. A 12-fold increase of caspase-2 activity was observed in GTN-treated Jurkat cells after 4h treatment and this was confirmed using Western blotting. Although the caspase-2 inhibitor Z-VDVAD-FMK inhibited the proteolytic activity of caspase-2, apoptosis ensued confirming that caspase-2 activity was not crucial for GTN-induced apoptosis. However, GTN-induced apoptosis was completely abrogated by N-acetylcysteine further confirming the role of oxidative stress. Since cytochrome c release was observed as early as 1h without any appreciable change in Bcl-2 protein expression, we further investigated whether overexpression of Bcl-2 confers resistance in GTN-induced cytotoxicity. Using a panel of Jurkat Bcl-2 transfectants, GTN cytotoxicity was not abrogated in these cells. In conclusion, GTN induces DNA damage and oxidative stress resulting in apoptosis which is independent of both caspase-2 and Bcl-2.
    Matched MeSH terms: Comet Assay
  11. Anticancer Activity and Molecular Mechanism of Polyphenol Rich Calophyllum inophyllum Fruit Extract in MCF-7 Breast Cancer Cells
    Shanmugapriya, Chen Y, Kanwar JR, Sasidharan S
    Nutr Cancer, 2017 10 25;69(8):1308-1324.
    PMID: 29068745 DOI: 10.1080/01635581.2017.1367944
    This study was conducted to investigate the anticancer effects and mechanism of Calophyllum inophyllum fruit extract against MCF-7 cells. C. inophyllum fruit extract was found to have markedly cytotoxic effect against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 23.59 µg/mL. Flow cytometry analysis revealed that C. inophyllum fruit extract mediated cell cycle at G0/G1 and G2/M phases, and MCF-7 cells entered the early phase of apoptosis. The expression of anti-apoptotic proteins Bcl-2 was decreased whereas the expression of the pro-apoptotic protein Bax, cytochrome C and p53 were increased after treatment. C. inophyllum fruit extract led to apoptosis in MCF-7 cells via the mitochondrial pathway in a dose dependent manner. This is evidenced by the elevation of intracellular ROS, the loss of mitochondria membrane potential (Δψm), and activation of caspase-3. Meanwhile, dose-dependent genomic DNA fragmentation was observed after C. inophyllum fruits extract treatment by comet assay. This study shows that C. inophyllum fruits extract-induced apoptosis is primarily p53 dependent and mediated through the activation of caspase-3. C. inophyllum fruit extract could be an excellent source of chemopreventive agent in the treatment of breast cancer and has potential to be explored as green anticancer agent.
    Matched MeSH terms: Comet Assay
  12. DNA Damage, Copper and Lead Associates with Cognitive Function among Older Adults
    Meramat A, Rajab NF, Shahar S, Sharif RA
    J Nutr Health Aging, 2017;21(5):539-545.
    PMID: 28448084 DOI: 10.1007/s12603-016-0759-1
    BACKGROUND: A cross sectional study was conducted in a group of 317 subjects older than 60 in Malaysia, aimed to determine risk factors associated with cognitive impairment in older adults, focusing on trace elements and DNA damage.

    METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels.

    RESULTS: A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05).

    CONCLUSION: High levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.

    Matched MeSH terms: Comet Assay
  13. Protection of hydroquinone-induced apoptosis by downregulation of Fau is mediated by NQO1
    Siew EL, Chan KM, Williams GT, Ross D, Inayat-Hussain SH
    Free Radic Biol Med, 2012 Oct 15;53(8):1616-24.
    PMID: 22687461 DOI: 10.1016/j.freeradbiomed.2012.05.046
    The Fau gene (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified as a potential tumor suppressor gene using a forward genetics approach. Downregulation of Fau by overexpression of its reverse sequence has been shown to inhibit apoptosis induced by DNA-damaging agents. To address a potential role of Fau in benzene toxicity, we investigated the apoptotic effects of hydroquinone (HQ), a major benzene metabolite, in W7.2 mouse thymoma cells transfected with either a plasmid construct expressing the antisense sequence of Fau (rfau) or the empty vector (pcDNA3.1) as a control. HQ induced apoptosis via increased production of reactive oxygen species and DNA damage, measured using dihydroethidine (HE) staining and alkaline Comet assay, respectively, in W7.2 pcDNA3.1 cells. In contrast, when Fau was downregulated by the antisense sequence in W7.2 rfau cells, HQ treatment did not cause DNA damage and oxidative stress and these cells were markedly more resistant to HQ-induced apoptosis. Further investigation revealed that there was an upregulation of NAD(P)H: quinone oxidoreductase 1 (NQO1), a detoxification enzyme for benzene-derived quinones, in W7.2 rfau cells. Compromising cellular NQO1 by use of a specific mechanism-based inhibitor (MAC 220) and NQO1 siRNA resensitized W7.2 rfau cells to HQ-induced apoptosis. Silencing of Fau in W7.2 wild-type cells resulted in increased levels of NQO1, confirming that downregulation of Fau results in NQO1 upregulation which protects against HQ-induced apoptosis.
    Matched MeSH terms: Comet Assay
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