Displaying publications 121 - 140 of 149 in total

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  1. Pratama E, Tian X, Lestari W, Iseki S, Ichwan SJ, Ikeda MA
    Biochem Biophys Res Commun, 2015 Dec;468(1-2):248-54.
    PMID: 26519881 DOI: 10.1016/j.bbrc.2015.10.121
    ARID3A and ARID3B are transcriptional targets of p53. Recently, it has been reported that ARID3A plays a critical role in the transcriptional activation of pro-arrest p21 in response to DNA damage. However, the role of ARID3B in the p53 regulatory pathway remains poorly understood. Here we show that ARID3A and ARID3B specifically bind to putative ARID3-binding sites in p53 target genes in vitro and in vivo. ARID3B and, to a lesser extent, ARID3A silencing blocked transcriptional activation of pro-apoptotic p53 target genes, such as PUMA, PIG3, and p53. Furthermore, ectopic ARID3B, to a lesser extent, ARID3A expression activated the pro-apoptotic gene expression, and only ARID3B induced apoptosis. Finally, ARID3B but not ARID3A silencing blocked apoptosis induction following DNA damage. These results indicated that, although ARID3B and ARID3A share overlapping functions, ARID3B play a key role in the expression of pro-apoptotic p53-target genes and apoptosis.
    Matched MeSH terms: DNA Damage
  2. Chan KM, Hamzah R, Rahaman AA, Jong VY, Khong HY, Rajab NF, et al.
    Food Chem Toxicol, 2012 Aug;50(8):2916-22.
    PMID: 22613213 DOI: 10.1016/j.fct.2012.04.048
    Inophyllin A (INO-A), a pyranoxanthone isolated from the roots of Calophyllum inophyllum represents a new xanthone with potential chemotherapeutic activity. In this study, the molecular mechanism of INO-A-induced cell death was investigated in Jurkat T lymphoblastic leukemia cells. Assessment of phosphatidylserine exposure confirmed apoptosis as the primary mode of cell death in INO-A-treated Jurkat cells. INO-A treatment for only 30 min resulted in a significant increase of tail moment which suggests that DNA damage is an early apoptotic signal. Further flow cytometric assessment of the superoxide anion level confirmed that INO-A induced DNA damage was mediated with a concomitant generation of reactive oxygen species (ROS). Investigation on the thiols revealed an early decrease of free thiols in 30 min after 50 μM INO-A treatment. Using tetramethylrhodamine ethyl ester, a potentiometric dye, the loss of mitochondrial membrane potential (MPP) was observed in INO-A-treated cells as early as 30 min. The INO-A-induced apoptosis progressed with the simultaneous activation of caspases-2 and -9 which then led to the processing of caspase-3. Taken together, these data demonstrate that INO-A induced early oxidative stress, DNA damage and loss of MMP which subsequently led to the activation of an intrinsic pathway of apoptosis in Jurkat cells.
    Matched MeSH terms: DNA Damage
  3. Joseph J, Khor KZ, Moses EJ, Lim V, Aziz MY, Abdul Samad N
    Int J Nanomedicine, 2021;16:3599-3612.
    PMID: 34079252 DOI: 10.2147/IJN.S303921
    Purpose: Vernonia amygdalina (VA) is a traditional African herbal medicine that has been reported to possess anticancer properties. However, the anticancer properties of VA silver nanoparticles have not been studied. The aim of the study was to examine and evaluate the anticancer activities of VA leaf extracts and VA silver nanoparticles on the human breast cancer cell line, MCF-7.

    Methods: VA leaves were extracted using sequential extraction assisted with ultrasound using three different solvents: ethanol, 50% ethanol, and deionized water. The silver nanoparticles were synthesised with VA aqueous extract.

    Results: The ethanol extract and VA silver nanoparticles inhibit MCF-7 cell proliferation with an average half-maximal inhibitory concentration (IC50) value of 67µg/mL and 6.11µg/mL, respectively, after 72 hours of treatment. The ethanol extract and VA silver nanoparticles also caused G1 phase cell cycle arrest, induced apoptosis and nuclear fragmentation in MCF-7 cells.

    Conclusion: VA ethanol extracts and VA silver nanoparticles decreased the cell viability in MCF-7 cells in a time and dose-dependent manner by inducing apoptosis and causing DNA damage. Further research is needed to elucidate the mechanism of action of VA leaf extracts and VA silver nanoparticles. This study is the first to report on the anticancer activity of VA silver nanoparticles in MCF-7 cells.

    Matched MeSH terms: DNA Damage
  4. Suzana Shahar, Kim, Tiu Teng, Nor Fadilah Rajab, Fatimah Arshad
    MyJurnal
    A preliminary study was conducted to determine the level of oxidative DNA damage, fruits and vegetables intake among 50 breast cancer patients (cases) as compared to 50 healthy women (controls) with no known medical history of breast cancer in Klang Valley. Both groups were matched for age and ethnicity. Data on socio-demographic, health status and medical history, fruits and vegetables intake, and supplements intake were obtained through an interviewbased questionnaire. Anthropometry measurements included weight, height, and waist and hip circumference were also carried out on subjects. A total of 3mL fasting venous blood was drawn to assess lymphocytes oxidative DNA damage using Alkaline Comet Assay. Results indicated that the mean intake of fruits and vegetables was lower in cases (4.09 ± 1.17 servings/d) than controls (4.77 ± 0.90 servings/d)(p < 0.05) The intake of fruits and vegetables from family groups of solanaceae, myrtaceae, caricaceae, apiaceae, brinjal, rutaceae, broccoli, orange, carrot, watermelon were 0.5 - 1 servings/week significantly higher among controls as compared to cases (p < 0.05 for all parameters). However, the intake of fruits from rosaceae family and apple was higher among controls than cases (p < 0.05). The estimated intake of ß-carotene, carotenoids, vitamin A, vitamin C (p < 0.001), a-carotene and lycopene (p < 0.05) from fruits and vegetables were higher among controls than cases. Mean DNA damage level of cases (4.55 ± 1.78 % DNA in tail, %TD; 0.35 ± 0.21 tail moment, TM) were 3.5 and 3.9 times higher than the value of controls (1.3 ± 0.70% TD; 0.09 ± 0.09 TM) (p < 0.001) and the damage increased with higher values of waist hip ratio (% TD, r = 0.396, p < 0.05; TM, r = 0.349, p < 0.05) and waist circumference (% TD, r = 0.334, p < 0.05; TM, r = 0.360, p < 0.05). There was an inverse relationship between oxidative DNA damage with intake of total fruits and vegetables, cauliflowers and water convolvulus and also consumption from rutaceae and solanaceae families. Similar trend was noted for estimated intake of vitamin A, carotenoids, vitamin C, ß-carotene and lycopene. In conclusion, the intake of fruits and vegetables of five servings/d and the consumption of specific families and types of fruits and vegetables might protect against oxidative DNA damage and further reduce breast cancer risk.
    Matched MeSH terms: DNA Damage
  5. Shahadin MS, Ab Mutalib NS, Latif MT, Greene CM, Hassan T
    Lung Cancer, 2018 04;118:69-75.
    PMID: 29572006 DOI: 10.1016/j.lungcan.2018.01.016
    Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.
    Matched MeSH terms: DNA Damage
  6. Achin NA, Kit TJ, Ngah WZW, Makpol S, Mazlan M, Hamezah HS, et al.
    Curr Aging Sci, 2018;11(3):182-194.
    PMID: 30338748 DOI: 10.2174/1874609811666181019141217
    BACKGROUND: Cognitive frailty emerges as one of the threats to healthy aging. It is in continuum with advancing of age with uncertain indicator between pathological and physiological changes. Alterations in pathways associated with the aging process have been observed including oxidative stress, lipid metabolism, and inflammation. However, the exact mechanisms leading to cognitive decline are still unclear.

    OBJECTIVE: This study was sought to assess the level of cognitive functions and linked with blood oxidative status during normal aging in rats.

    METHODS: A longitudinal study using male Sprague Dawley rats was performed starting from the age of 14 months old to 27 months old. Cognitive functions tests such as open field, Morris water maze and object recognition were determined at the age of 14, 18, 23, and 27 months old and were compared with group 3 months old. Blood was collected from the orbital venous sinus and oxidative status was determined by measuring the level of DNA damage, lipid peroxidation, protein oxidation and antioxidant enzymes activity.

    RESULTS: Aged rats showed declining exploratory behavior and increased in the level of anxiety as compared to the young rats. The level of DNA damage increased with increasing age. Interestingly, our study found that both levels of malondialdehyde and plasma carbonyl content decreased with age. In addition, the level of superoxide dismutase activity was significantly decreased with age whereas catalase activity was significantly increased from 18 months of age. However, no significant difference was found in glutathione peroxidase activity among all age groups.

    CONCLUSION: The progressions of cognitive impairment in normal aging rats are linked to the increment in the level of DNA damage.

    Matched MeSH terms: DNA Damage
  7. Ooi TC, Chan KM, Sharif R
    Free Radic Res, 2020 May;54(5):330-340.
    PMID: 32366187 DOI: 10.1080/10715762.2020.1763333
    Zinc L-carnosine (ZnC) is a chelated compound of zinc and L-carnosine. The present study aims to determine the protective effects of ZnC against hydrogen peroxide (H2O2)-induced oxidative stress and genomic damage in CCD-18co human normal colon fibroblast cells. Generally, cells were pretreated with ZnC (0-100 µM) for 24 h before challenged with 20 µM of H2O2 for 1 h to induce oxidative damage. Results showed that pretreatment with ZnC was able to reduce the intracellular ROS level in CCD-18co cells after being challenged with H2O2. Moreover, pretreatment with ZnC demonstrated protection from H2O2-induced DNA strand breaks and micronucleus formation. Our current findings revealed that pretreatment with ZnC could induce the activation of MTF-1 signaling pathway and expression of metallothionein (MT) in a dose-dependent manner. However, ZnC did not have any effects on Nrf2 signaling pathway and the expression of glutathione, superoxide dismutase 1, and glutamate-cysteine ligase catalytic subunit (GCLC). Furthermore, pretreatment with ZnC did not induce the expression of OGG1 and PARP-1 in CCD-18co cells, suggesting that these two DNA repairing enzymes are not related to the genoprotective effects of ZnC. Since the expression of MT has been demonstrated to protect cells from oxidative DNA damage induced by various genotoxic agents, the genoprotective effects of ZnC might be due to the ability of ZnC to induce the expression of MT. In conclusion, ZnC pretreatment was able to protect CCD-18co cells from H2O2-induced genomic damage via the activation of the MTF-1 signalling pathway and the induction of MT expression.
    Matched MeSH terms: DNA Damage
  8. Jaudan A, Sharma S, Malek SNA, Dixit A
    PLoS One, 2018;13(2):e0191523.
    PMID: 29420562 DOI: 10.1371/journal.pone.0191523
    Pinostrobin (PN) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if PN induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that PN at increasing dose effectivity reduced the cell viability as well as GSH and NO2- levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in PN induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after PN treatment showed involvement of free radicals, which in turn further augment ROS levels. PN treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in PN-treated cells suggested that PN induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.
    Matched MeSH terms: DNA Damage
  9. Inayat-Hussain SH, Wong LT, Chan KM, Rajab NF, Din LB, Harun R, et al.
    Toxicol Lett, 2009 Dec 15;191(2-3):118-22.
    PMID: 19698770 DOI: 10.1016/j.toxlet.2009.08.012
    Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Overexpression of full-length receptor for activated protein C-kinase 1 (RACK-1) and pc3n3, which up-regulates endogenous RACK-1, in both Jurkat and W7.2 T cells resulted in inhibition of goniothalamin-induced cell death as assessed by MTT and clonogenic assays. However, overexpression of rFau (antisense sequence to Finkel-Biskis-Reilly murine sarcoma virus-associated ubiquitously expressed gene) in W7.2 cells did not confer resistance to goniothalamin-induced cell death. Etoposide, a clinically used cytotoxic agent, was equipotent in causing cytotoxicity in all the stable transfectants. Assessment of DNA damage by Comet assay revealed goniothalamin-induced DNA strand breaks as early as 1 h in vector control but this effect was inhibited in RACK-1 and pc3n3 stably transfected W7.2 cells. This data demonstrate that RACK-1 plays a crucial role in regulating cell death signalling pathways induced by goniothalamin.
    Matched MeSH terms: DNA Damage
  10. Makpol S, Durani LW, Chua KH, Mohd Yusof YA, Ngah WZ
    J Biomed Biotechnol, 2011;2011:506171.
    PMID: 21541185 DOI: 10.1155/2011/506171
    This study determined the molecular mechanisms of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs). Primary culture of HDFs at various passages were incubated with 0.5 mg/mL TRF for 24 h. Telomere shortening with decreased telomerase activity was observed in senescent HDFs while the levels of damaged DNA and number of cells in G(0)/G(1) phase were increased and S phase cells were decreased. Incubation with TRF reversed the morphology of senescent HDFs to resemble that of young cells with decreased activity of SA-β-gal, damaged DNA, and cells in G(0)/G(1) phase while cells in the S phase were increased. Elongated telomere length and restoration of telomerase activity were observed in TRF-treated senescent HDFs. These findings confirmed the ability of tocotrienol-rich fraction in preventing HDFs cellular ageing by restoring telomere length and telomerase activity, reducing damaged DNA, and reversing cell cycle arrest associated with senescence.
    Matched MeSH terms: DNA Damage
  11. Gill MR, Harun SN, Halder S, Boghozian RA, Ramadan K, Ahmad H, et al.
    Sci Rep, 2016 08 25;6:31973.
    PMID: 27558808 DOI: 10.1038/srep31973
    Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.
    Matched MeSH terms: DNA Damage/drug effects; DNA Damage/radiation effects
  12. 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: DNA Damage
  13. Khan S, Zakariah M, Palaniappan S
    Tumour Biol., 2016 Aug;37(8):10805-13.
    PMID: 26874727 DOI: 10.1007/s13277-016-4970-9
    Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies.
    Matched MeSH terms: DNA Damage
  14. 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: DNA Damage
  15. 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: DNA Damage
  16. Ooi TC, Meramat A, Rajab NF, Shahar S, Ismail IS, Azam AA, et al.
    Nutrients, 2020 Aug 30;12(9).
    PMID: 32872655 DOI: 10.3390/nu12092644
    Intermittent fasting (IF) refers to various dietary regimens that cycle between a period of non-fasting and a period of total fasting. This study aimed to determine the effects of IF on cognitive function among elderly individuals who practice IF who have mild cognitive impairment (MCI). A total of 99 elderly subjects with MCI of Malay ethnicity without any terminal illness were recruited from a larger cohort study, LRGS TUA. The subjects were divided into three groups, comprising those who were regularly practicing IF (r-IF), irregularly practicing IF (i-IF), and non-fasters (n-IF). Upon 36 months of follow-up, more MCI subjects in the r-IF group reverted to successful aging with no cognitive impairment and diseases (24.3%) compared to those in i-IF (14.2%) and n-IF groups (3.7%). The r-IF group's subjects exhibited significant increment in superoxide dismutase (SOD) activity and reduction in body weight, levels of insulin, fasting blood glucose, malondialdehyde (MDA), C-reactive protein (CRP), and DNA damage. Moreover, metabolomics analysis showed that IF may modulate cognitive function via various metabolite pathways, including the synthesis and degradation of ketone bodies, butanoate metabolism, pyruvate metabolism, and glycolysis and gluconeogenesis pathways. Overall, the MCI-afflicted older adults who practiced IF regularly had better cognitive scores and reverted to better cognitive function at 36 months follow-up.
    Matched MeSH terms: DNA Damage
  17. Adenan MNH, Yazan LS, Christianus A, Md Hashim NF, Mohd Noor S, Shamsudin S, et al.
    Molecules, 2021 Mar 12;26(6).
    PMID: 33809054 DOI: 10.3390/molecules26061557
    Large doses of ionizing radiation can damage human tissues. Therefore, there is a need to investigate the radiation effects as well as identify effective and non-toxic radioprotectors. This study evaluated the radioprotective effects of Kelulut honey (KH) from stingless bee (Trigona sp.) on zebrafish (Danio rerio) embryos. Viable zebrafish embryos at 24 hpf were dechorionated and divided into four groups, namely untreated and non-irradiated, untreated and irradiated, KH pre-treatment and amifostine pre-treatment. The embryos were first treated with KH (8 mg/mL) or amifostine (4 mM) before irradiation at doses of 11 Gy to 20 Gy using gamma ray source, caesium-137 (137Cs). Lethality and abnormality analysis were performed on all of the embryos in the study. Immunohistochemistry assay was also performed using selected proteins, namely γ-H2AX and caspase-3, to investigate DNA damages and incidences of apoptosis. KH was found to reduce coagulation effects at up to 20 Gy in the lethality analysis. The embryos developed combinations of abnormality, namely microphthalmia (M), body curvature and microphthalmia (BM), body curvature with microphthalmia and microcephaly (BMC), microphthalmia and pericardial oedema (MO), pericardial oedema (O), microphthalmia with microcephaly and pericardial oedema (MCO) and all of the abnormalities (AA). There were more abnormalities developed from 24 to 72 h (h) post-irradiation in all groups. At 96 h post-irradiation, KH was identified to reduce body curvature effect in the irradiated embryos (up to 16 Gy). γ-H2AX and caspase-3 intensities in the embryos pre-treated with KH were also found to be lower than the untreated group at gamma irradiation doses of 11 Gy to 20 Gy and 11 Gy to 19 Gy, respectively. KH was proven to increase the survival rate of zebrafish embryos and exhibited protection against organ-specific abnormality. KH was also found to possess cellular protective mechanism by reducing DNA damage and apoptosis proteins expression.
    Matched MeSH terms: DNA Damage
  18. 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: DNA Damage
  19. 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: DNA Damage
  20. Yap LF, Lai SL, Patmanathan SN, Gokulan R, Robinson CM, White JB, et al.
    Sci Rep, 2016 Dec 09;6:38758.
    PMID: 27934959 DOI: 10.1038/srep38758
    Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis.
    Matched MeSH terms: DNA Damage
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