Displaying publications 41 - 51 of 51 in total

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  1. 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: Mutagens/toxicity*
  2. Fulltext Cytoprotective effects of (E)-N-(2-(3, 5-dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) against 4-nitroquinoline 1-oxide-induced damage in CCD-18Co human colon fibroblast cells
    Tan HH, Thomas NF, Inayat-Hussain SH, Chan KM
    PLoS One, 2020;15(5):e0223344.
    PMID: 32365104 DOI: 10.1371/journal.pone.0223344
    Stilbenes are a group of chemicals characterized with the presence of 1,2-diphenylethylene. Previously, our group has demonstrated that synthesized (E)-N-(2-(3, 5-dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) possesses potential chemopreventive activity specifically inducing NAD(P)H:quinone oxidoreductase 1 (NQO1) protein expression and activity. In this study, the cytoprotective effects of BK3C231 on cellular DNA and mitochondria were investigated in normal human colon fibroblast, CCD-18Co cells. The cells were pretreated with BK3C231 prior to exposure to the carcinogen 4-nitroquinoline 1-oxide (4NQO). BK3C231 was able to inhibit 4NQO-induced cytotoxicity. Cells treated with 4NQO alone caused high level of DNA and mitochondrial damages. However, pretreatment with BK3C231 protected against these damages by reducing DNA strand breaks and micronucleus formation as well as decreasing losses of mitochondrial membrane potential (ΔΨm) and cardiolipin. Interestingly, our study has demonstrated that nitrosative stress instead of oxidative stress was involved in 4NQO-induced DNA and mitochondrial damages. Inhibition of 4NQO-induced nitrosative stress by BK3C231 was observed through a decrease in nitric oxide (NO) level and an increase in glutathione (GSH) level. These new findings elucidate the cytoprotective potential of BK3C231 in human colon fibroblast CCD-18Co cell model which warrants further investigation into its chemopreventive role.
    Matched MeSH terms: Mutagens/toxicity*
  3. Genotoxicity assessment of raw and treated water samples using Allium cepa assay: evidence from Perak River, Malaysia
    Malakahmad A, Manan TSBA, Sivapalan S, Khan T
    Environ Sci Pollut Res Int, 2018 Feb;25(6):5421-5436.
    PMID: 29209979 DOI: 10.1007/s11356-017-0721-8
    Allium cepa assay was carried out in this study to evaluate genotoxic effects of raw and treated water samples from Perak River in Perak state, Malaysia. Samples were collected from three surface water treatment plants along the river, namely WTPP, WTPS, and WTPK. Initially, triplicates of equal size Allium cepa (onions) bulbs, 25-30 mm in diameter and average weight of 20 g, were set up in distilled water for 24 h at 20 ± 2 °C and protected from direct sunlight, to let the roots to grow. After germination of roots (0.5-1.0 cm in length), bulbs were transferred to collected water samples each for a 96-h period of exposure. The root physical deformations were observed. Genotoxicity quantification was based on mitotic index and genotoxicity level. Statistical analysis using cross-correlation function for replicates from treated water showed that root length has inverse correlation with mitotic indices (r = - 0.969) and frequencies of cell aberrations (r = - 0.976) at lag 1. Mitotic indices and cell aberrations of replicates from raw water have shown positive correlation at lag 1 (r = 0.946). Genotoxicity levels obtained were 23.4 ± 1.98 (WTPP), 26.68 ± 0.34 (WTPS), and 30.4 ± 1.13 (WTPK) for treated water and 17.8 ± 0.18 (WTPP), 37.15 ± 0.17 (WTPS), and 47.2 ± 0.48 (WTPK) for raw water. The observed cell aberrations were adherence, chromosome delay, C-metaphase, chromosome loss, chromosome bridge, chromosome breaks, binucleated cell, mini cell, and lobulated nuclei. The morphogenetic deformations obtained were likely due to genotoxic substances presence in collected water samples. Thus, water treatment in Malaysia does not remove genotoxic compounds.
    Matched MeSH terms: Mutagens/toxicity*
  4. Fulltext Evaluation of the genotoxicity of zerumbone in cultured human peripheral blood lymphocytes
    Al-Zubairi AS, Abdul AB, Syam MM
    Toxicol In Vitro, 2010 Apr;24(3):707-12.
    PMID: 20123012 DOI: 10.1016/j.tiv.2010.01.011
    The chromosomal aberrations (CA) assay and micronucleus (MN) test were employed to investigate the effect in vitro of zerumbone (ZER) on human chromosomes. ZER is a sesquiterpene compound isolated from the rhizomes of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are employed as a traditional medicine for some ailments and as condiments. ZER has been shown to have anti-cancer and apoptosis-inducing properties against various human tumour cells. It has also been shown to be active in vivo against a number of induced malignancies. Studies on ZER genotoxicity in cultured human peripheral blood lymphocytes (PBL) have not been reported so far. Therefore, the present study was undertaken to investigate the ability of ZER to induce chromosomal aberrations and micronuclei formation in human lymphocytes in vitro. Human blood samples were obtained from four healthy, non-smoking males aged 25-35years. Cultures were exposed to the drug for 48h at four final concentrations: 10, 20, 40 and 80 microM. Mitomycin C (MMC) was used as a positive control. The results of chromosomal aberrations assay showed that ZER was not clastogenic, when compared to untreated control, meanwhile MN test results showed a dose-dependent increase in MN formation. The overall clastogenic effect of ZER on human PBL was statistically not significant. In conclusion, ZER is a cytotoxic but not a clastogenic substance in human PBL.
    Matched MeSH terms: Mutagenicity Tests; Mutagens*
  5. Effects of Perivitelline Fluid Obtained from Horseshoe Crab on The Proliferation and Genotoxicity of Dental Pulp Stem Cells
    Musa M, Mohd Ali K, Kannan TP, Azlina A, Omar NS, Chatterji A, et al.
    Cell J, 2015;17(2):253-63.
    PMID: 26199904
    OBJECTIVE: Perivitelline fluid (PVF) of the horseshoe crab embryo has been reported to possess an important role during embryogenesis by promoting cell proliferation. This study aims to evaluate the effect of PVF on the proliferation, chromosome aberration (CA) and mutagenicity of the dental pulp stem cells (DPSCs).

    MATERIALS AND METHODS: This is an in vitro experimental study. PVF samples were collected from horseshoe crabs from beaches in Malaysia and the crude extract was prepared. DPSCs were treated with different concentrations of PVF crude extract in an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (cytotoxicity test). We choose two inhibitory concentrations (IC50 and IC25) and two PVF concentrations which produced more cell viability compared to a negative control (100%) for further tests. Quantitative analysis of the proliferation activity of PVF was studied using the AlamarBlue®assay for 10 days. Population doubling times (PDTs) of the treatment groups were calculated from this assay. Genotoxicity was evaluated based on the CA and Ames tests. Statistical analysis was carried out using independent t test to calculate significant differences in the PDT and mitotic indices in the CA test between the treatment and negative control groups. Significant differences in the data were P<0.05.

    RESULTS: A total of four PVF concentrations retrieved from the MTT assay were 26.887 mg/ml (IC50), 14.093 mg/ml (IC25), 0.278 mg/ml (102% cell viability) and 0.019 mg/ml (102.5% cell viability). According to the AlamarBlue®assay, these PVF groups produced comparable proliferation activities compared to the negative (untreated) control. PDTs between PVF groups and the negative control were insignificantly different (P>0.05). No significant aberrations in chromosomes were observed in the PVF groups and the Ames test on the PVF showed the absence of significant positive results.

    CONCLUSION: PVF from horseshoe crabs produced insignificant proliferative activity on treated DPSCs. The PVF was non-genotoxic based on the CA and Ames tests.

    Matched MeSH terms: Mutagens
  6. Fulltext Microbiome and colorectal cancer: an overview and local perspective
    Rahman Jamal
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):4-4.
    MyJurnal
    Colorectal cancer (CRC) is an important health problem that is on the rise globally, where it is the fourth most com-mon cause of deaths from cancer. CRC is now the 2nd commonest cancer in men and 3rd commonest in women in Malaysia. Diet, lifestyle, genetics and environmental interaction, together with underlying gut conditions such as inflammatory bowel disease have been reported to contribute to the disease. In addition, the gut microbiome has also been increasingly reported to be associated with CRC development, with dysbiosis of the commensal bacteria ob-served in CRC patients. Bacterial genera such as Bacteroides, Fusobacterium and Prevotella are more commonly de-tected in CRC patients compared to healthy individuals. Nevertheless, not much is known about the gut microbiome among Malaysians with different ethnicities. In Malaysia, the Chinese has the highest incidence of CRC, followed by Malays and Indians. The reason behind this difference may be contributed by the differences in the dietary intake that could modulate the gut microbiome and contribute towards the development of CRC. The current knowledge on this field still much depends on reports from individuals of American, European, Chinese, Brazilian and Japanese descendants in origin. The oncogenic potential of bacteria was suggested to include inflammation and the produc-tion of mutagenic toxin. A significant increase in certain intestinal microbiota including the genuses Enteroccus and Streptococcus spp. was detected in the advanced stage of colorectal adenoma. However, there are discrepancies in the previous studies, where some bacteria genera might be over-reported or underestimated. It is likely that the gut microbiome differs between populations. There is also no available data on the gut microbiome of the healthy individuals, colorectal adenoma (pre-cancerous) and colorectal cancer patients in the Malaysian population. Recent advancements in next generation sequencing allow faster and more accurate determination of microbial consortium in various niches of the human body and environment. In particular, sequencing of the 16S rRNA gene with specific primers have been reported to allow accurate determination of bacterial orders commonly found in the human gut as well as for those which are not expected in the digestive system. Recent developments in gut microbiome DNA ex-traction also contributed to the robustness of gut microbiome determination and analysis. All the above will contrib-ute towards an accurate and rapid cataloging process of the Malaysian gut microbiome and also enable comparison between healthy individuals, colorectal adenoma and CRC patients of the Malaysian population.
    Matched MeSH terms: Mutagens
  7. Fulltext Saprophytic yeasts: effective biocontrol agents against Aspergillus flavus
    Afsah-Hejri, L.
    International Food Research Journal, 2013;20(6):3403-3409.
    MyJurnal
    Aflatoxins are carcinogenic, mutagenic and teratogenic fungal toxins predominantly produced by Aspergillus flavus (A. flavus) and Aspergillus parasiticus (A. parasiticus). Members of the Aspergillus family are wound-invading pathogens that can infect pistachio trees and nuts. The pistachio nut is a favorite tree nut worldwide, and more than half of the world’s pistachio production is from Iran. Pistachio nuts can easily be infected with Aspergillus spp. due to early splitting or due to animal, insect or physical damage. Any established infection of Aspergillus under high relative humidity and temperature results in the production and rapid accumulation of aflatoxins in pistachio nuts. It is impractical to remove aflatoxins from pistachio nuts after they are produced. Some microorganisms (such as saprophytic yeasts) have been reported to have an antagonistic effect against Aspergillus spp. This study aimed to isolate saprophytic yeasts from pistachio fruits and leaves and investigate their biocontrol activities against a toxigenic strain of Aspergillus flavus (A. flavus). Saprophytic yeasts were identified based on their morphological properties and biochemical tests. In total, 24 yeast isolates were obtained from pistachio fruits and leaves, and their antagonistic effect on A. flavus (PTCC 5006) was investigated. Five saprophytic yeast isolates, displaying the highest biocontrol activities against A. flavus (PTCC 5006), were identified as Pseudozyma fusiformata, Cryptococcus albidus, Rhodotorula fragaria, Cryptococcus hungaricus and Rhodotorula hinula. The biocontrol activities of these yeast isolates were evaluated by their inhibitory effects on sporulation, colony expansion, biomass production and prevention of aflatoxin B1 (AFB1) production. Pseudozyma fusiformata was the most effective yeast isolate in terms of spore reduction (84.6%) and inhibition of AFB1 production (89.1%). Cryptococcus albidus produced the maximum reduction in fungal dry weight (77.9%). Based on these results, isolated saprophytic yeasts from pistachio fruits and leaves can be used as effective biocontrol agents against the growth of Aspergillus and aflatoxin production.
    Matched MeSH terms: Mutagens
  8. Fulltext Genotoxic evaluation of synthetic hydroxyapatite using mammalian bone marrow chromosome aberration test
    Kannan, Thirumulu Ponnuraj, Nik Ahmad Shah Nik Lah, Azlina Ahmad, Siti Fatimah Ramli, Narazah Mohd Yusof, Ab Rani Samsudin
    Archives of Orofacial Sciences, 2014;9(1):1-7.
    MyJurnal
    Some of the beneficial bio compatible properties of hydroxyapatite [Ca10(PO4)6(OH)2]; the major componentand an essential ingredient of normal bone and teeth, are that it is rapidly integrated into the human body and will bondto bone forming in distinguishable unions. But, before new materials are approved for medical use, mutagenesis systems to exclude cytotoxic, mutagenic or carcinogenic properties are applied worldwide. This study aimed to detectany chromosomal aberrations induced by the synthetic hydroxyapatite granules [Manufactured by Universiti Sains
    Malaysia, (USM) Penang, Malaysia] in the bone marrow cells of mice. The mitotic indices of the groups treated with synthetic hydroxya patite granules did not show any significant difference as compared to the negative control group treated with distilled water. Also the groups of mice treated with synthetic hydroxyapatite granules and distilled waterdid not induce significant change in chromosome aberrations as compared to the positive control group treated with Mitomycin C. The mitotic indices and chromosomal analyses indicate that under the present test conditions, synthetichydroxya patite granules (manufactured by USM) are non cytotoxic and do not induce chromosome aberrations in the bone marrow cells of mice.
    Matched MeSH terms: Mutagens
  9. In vitro genotoxicity tests for polyhydroxybutyrate--a synthetic biomaterial
    Ali AQ, Kannan TP, Ahmad A, Samsudin AR
    Toxicol In Vitro, 2008 Feb;22(1):57-67.
    PMID: 17892925
    The aims of this study are to determine the mutagenicity of a locally produced polyhydroxybutyrate (PHB) using Salmonella mutagenicity test and to find out if PHB altered the expression of p53 and c-myc proto-oncogenes and bcl-xl and bcl-xs anti-apoptotic genes in the human fibroblast cell line, MRC-5. Different concentrations of PHB were incubated with special genotypic variants of Salmonella strains (TA1535, TA1537, TA1538, TA98 and TA100) carrying mutations in several genes both with and without metabolic activation (S9) and the test was assessed based on the number of revertant colonies. The average number of revertant colonies per plate treated with PHB was less than double as compared to that of negative control. For the gene expression analyses, fibroblast cell lines were treated with PHB at different concentrations and incubated for 1, 12, 24 and 48 h separately. The total RNA was isolated and analysed for the expression of p53, c-myc, bcl-xl and bcl-xs genes. The PHB did not show over or under expression of the genes studied. The above tests indicate that the locally produced PHB is non-genotoxic and does not alter the expression of the proto-oncogenes and anti-apoptotic genes considered in this study.
    Matched MeSH terms: Mutagens/toxicity*
  10. 50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C
    Al-Dualimi DW, Shah Abdul Majid A, Al-Shimary SFF, Al-Saadi AA, Al Zarzour R, Asif M, et al.
    Drug Chem Toxicol, 2018 Jan;41(1):82-88.
    PMID: 28635332 DOI: 10.1080/01480545.2017.1317785
    Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens. Orthosiphon stamineus (O.s) also known as Cat whiskers. The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect. The study aimed to evaluate the effects of different doses (250, 500 and 1000 mg kg-1) of 50% ethanol extract of O.s (Et. O.s) on micro-nucleated polychromatic erythrocytes (MNPCE), Polychromatic to normachromatic erythrocytes ratio (PCE/NCE), Mitotic index (MI), and Chromosomal aberration (CA) in Bab/c mice. Moreover, these parameters were used to evaluate the anti-genotoxic and clastogenic potencies of (Et. O.s) against mitomycin c (MMC) that interact with biological molecules and induce genotoxic and clastogenic disorders in non-tumor cells. MMC (4 mg kg-1) was injected intraperitoneally (i.p.) to the mice before and after treatment with three different doses of (Et. O.s). The results indicated that the extract at different doses did not show significant (p ≥ 0.05) differences in (MNPCE), (PCE/NCE) ratios, and (CA) values. The higher doses sowed high (MI) values compared with untreated control group. MMC showed significant increase (p ≤ 0.001) in (MNPCE), (CA) and reduce (PCE/NCE) and (MI) values compared with untreated control group. Treatment with (Et. O.s) at different doses before and after MMC injection showed to modulate MNPCE, PCE/NCE ratios, CA and MI values in mice bone marrow cells suggesting genoprotective potential of this plant extract.
    Matched MeSH terms: Mutagens/toxicity*
  11. Fulltext Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies
    Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.
    ACS Omega, 2021 Jan 12;6(1):265-277.
    PMID: 33458478 DOI: 10.1021/acsomega.0c04461
    In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
    Matched MeSH terms: Mutagens
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