Displaying publications 41 - 60 of 110 in total

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  1. Fulltext Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
    Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S254-96.
    PMID: 26106142 DOI: 10.1093/carcin/bgv039
    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
    Matched MeSH terms: Carcinogens, Environmental/adverse effects*
  2. Predicting points of departure for risk assessment based on in vitro cytotoxicity data and physiologically based kinetic (PBK) modeling: The case of kidney toxicity induced by aristolochic acid I
    Abdullah R, Alhusainy W, Woutersen J, Rietjens IM, Punt A
    Food Chem Toxicol, 2016 Jun;92:104-16.
    PMID: 27016491 DOI: 10.1016/j.fct.2016.03.017
    Aristolochic acids are naturally occurring nephrotoxins. This study aims to investigate whether physiologically based kinetic (PBK) model-based reverse dosimetry could convert in vitro concentration-response curves of aristolochic acid I (AAI) to in vivo dose response-curves for nephrotoxicity in rat, mouse and human. To achieve this extrapolation, PBK models were developed for AAI in these different species. Subsequently, concentration-response curves obtained from in vitro cytotoxicity models were translated to in vivo dose-response curves using PBK model-based reverse dosimetry. From the predicted in vivo dose-response curves, points of departure (PODs) for risk assessment could be derived. The PBK models elucidated species differences in the kinetics of AAI with the overall catalytic efficiency for metabolic conversion of AAI to aristolochic acid Ia (AAIa) being 2-fold higher for rat and 64-fold higher for mouse than human. Results show that the predicted PODs generally fall within the range of PODs derived from the available in vivo studies. This study provides proof of principle for a new method to predict a POD for in vivo nephrotoxicity by integrating in vitro toxicity testing with in silico PBK model-based reverse dosimetry.
    Matched MeSH terms: Carcinogens/toxicity*
  3. Carcinogenic and non-carcinogenic health risk of arsenic ingestion via drinking water in Langat River Basin, Malaysia
    Ahmed MF, Mokhtar MB, Alam L
    Environ Geochem Health, 2021 Feb;43(2):897-914.
    PMID: 32372251 DOI: 10.1007/s10653-020-00571-w
    The prolonged persistence of toxic arsenic (As) in environment is due to its non-biodegradable characteristic. Meanwhile, several studies have reported higher concentrations of As in Langat River. However, it is the first study in Langat River Basin, Malaysia, that As concentrations in drinking water supply chain were determined simultaneously to predict the health risks of As ingestion. Water samples collected in 2015 from the four stages of drinking water supply chain were analysed for As concentration by inductively coupled plasma mass spectrometry. Determined As concentrations along with the time series data (2004-2015) were significantly within the maximum limit 0.01 mg/L of drinking water quality standard set by World Health Organization. The predicted As concentration by auto-regression moving average was 3.45E-03 mg/L in 2020 at 95% level based on time series data including climatic control variables. Long-term As ingestion via household filtration water at Langat Basin showed no potential lifetime cancer risk (LCR) 9.7E-06 (t = 6.68; p = 3.37E-08) as well as non-carcinogenic hazard quotient (HQ) 4.8E-02 (t = 6.68; p = 3.37E-08) risk at 95% level. However, the changing landscape, ex-mining ponds and extensive use of pesticides for palm oil plantation at Langat Basin are considered as the major sources of increased As concentration in Langat River. Therefore, a two-layer water filtration system at Langat Basin should be introduced to accelerate the achievement of sustainable development goal of getting safe drinking water supply.
    Matched MeSH terms: Carcinogens, Environmental/analysis*
  4. Biomedical Applications of Aromatic Azo Compounds
    Ali Y, Hamid SA, Rashid U
    Mini Rev Med Chem, 2018;18(18):1548-1558.
    PMID: 29792144 DOI: 10.2174/1389557518666180524113111
    Azo dyes are widely used in textile, fiber, cosmetic, leather, paint and printing industries. Besides their characteristic coloring function, azo compounds are reported as antibacterial, antiviral, antifungal and cytotoxic agents. They have the ability to be used as drug carriers, either by acting as a 'cargo' that entrap therapeutic agents or by prodrug approach. The drug is released by internal or external stimuli in the region of interest, as observed in colon-targeted drug delivery. Besides drug-like and drug carrier properties, a number of azo dyes are used in cellular staining to visualize cellular components and metabolic processes. However, the biological significance of azo compounds, especially in cancer chemotherapy, is still in its infancy. This may be linked to early findings that declared azo compounds as one of the possible causes of cancer and mutagenesis. Currently, researchers are screening the aromatic azo compounds for their potential biomedical use, including cancer diagnosis and therapy. In this review, we highlight the medical applications of azo compounds, particularly related to cancer research. The biomedical significance of cis-trans interchange and negative implications of azo compounds are also discussed in brief.
    Matched MeSH terms: Carcinogens/toxicity
  5. Estimation of the dietary intake and risk assessment of food carcinogens (3-MCPD and 1,3-DCP) in soy sauces by Monte Carlo simulation
    Wong SF, Lee BQ, Low KH, Jenatabadi HS, Wan Mohamed Radzi CWJB, Khor SM
    Food Chem, 2020 May 01;311:126033.
    PMID: 31869642 DOI: 10.1016/j.foodchem.2019.126033
    Quantifiable levels of 3-chloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) were found in domestically manufactured soy-based sauces. Selected commercial foods in the Malaysian market (n = 43) were analyzed for their 3-MCPD and 1,3-DCP contents using a validated gas chromatography-mass spectrometry technique. The 3-MCPD and 1,3-DCP contents of the analyzed food samples varied from not detectable levels to 0.1223 ± 0.0419 mg kg-1 and not detectable levels to 0.025 ± 0.0041 mg kg-1, respectively. High concentrations of 3-MCPD, exceeding Malaysia's maximum tolerable limit of 0.02 mg kg-1, were found in chicken seasoning cubes (mean = 0.0898 ± 0.0378 mg kg-1). Monte Carlo simulation-based health risk assessment revealed that 3-MCPD and 1,3-DCP intakes in the 50th, 95th, and 99th percentiles were lower than 4 µg kg-1 bw day-1, the limit recommended by JECFA in 2016. Hence, it was concluded that the exposure of Malaysian citizens to chloropropanols through soy sauce consumption does not present a health risk.
    Matched MeSH terms: Carcinogens/analysis*
  6. Status, source identification, and health risks of potentially toxic element concentrations in road dust in a medium-sized city in a developing country
    Praveena SM, Aris AZ
    Environ Geochem Health, 2018 Apr;40(2):749-762.
    PMID: 28929262 DOI: 10.1007/s10653-017-0021-8
    This study aims to determine the status of potentially toxic element concentrations of road dust in a medium-sized city (Rawang, Malaysia). This study adopts source identification via enrichment factor, Pearson correlation analysis, and Fourier spectral analysis to identify sources of potentially toxic element concentrations in road dust in Rawang City, Malaysia. Health risk assessment was conducted to determine potential health risks (carcinogenic and non-carcinogenic risks) among adults and children via multiple pathways (i.e., ingestion, dermal contact, and inhalation). Mean of potentially toxic element concentrations were found in the order of Pb > Zn > Cr(IV) > Cu > Ni > Cd > As > Co. Source identification revealed that Cu, Cd, Pb, Zn, Ni, and Cr(IV) are associated with anthropogenic sources in industrial and highly populated areas in northern and southern Rawang, cement factories in southern Rawang, as well as the rapid development and population growth in northwestern Rawang, which have resulted in high traffic congestion. Cobalt, Fe, and As are related to geological background and lithologies in Rawang. Pathway orders for both carcinogenic and non-carcinogenic risks are ingestion, dermal contact, and inhalation, involving adults and children. Non-carcinogenic health risks in adults were attributed to Cr(IV), Pb, and Cd, whereas Cu, Cd, Cr(IV), Pb, and Zn were found to have non-carcinogenic health risks for children. Cd, Cr(IV), Pb, and As may induce carcinogenic risks in adults and children, and the total lifetime cancer risk values exceeded incremental lifetime.
    Matched MeSH terms: Carcinogens/toxicity
  7. Mosquito coil emissions and health implications
    Liu W, Zhang J, Hashim JH, Jalaludin J, Hashim Z, Goldstein BD
    Environ Health Perspect, 2003 Sep;111(12):1454-60.
    PMID: 12948883
    Burning mosquito coils indoors generates smoke that can control mosquitoes effectively. This practice is currently used in numerous households in Asia, Africa, and South America. However, the smoke may contain pollutants of health concern. We conducted the present study to characterize the emissions from four common brands of mosquito coils from China and two common brands from Malaysia. We used mass balance equations to determine emission rates of fine particles (particulate matter < 2.5 microm in diameter; PM(2.5)), polycyclic aromatic hydrocarbons (PAHs), aldehydes, and ketones. Having applied these measured emission rates to predict indoor concentrations under realistic room conditions, we found that pollutant concentrations resulting from burning mosquito coils could substantially exceed health-based air quality standards or guidelines. Under the same combustion conditions, the tested Malaysian mosquito coils generated more measured pollutants than did the tested Chinese mosquito coils. We also identified a large suite of volatile organic compounds, including carcinogens and suspected carcinogens, in the coil smoke. In a set of experiments conducted in a room, we examined the size distribution of particulate matter contained in the coil smoke and found that the particles were ultrafine and fine. The findings from the present study suggest that exposure to the smoke of mosquito coils similar to the tested ones can pose significant acute and chronic health risks. For example, burning one mosquito coil would release the same amount of PM(2.5) mass as burning 75-137 cigarettes. The emission of formaldehyde from burning one coil can be as high as that released from burning 51 cigarettes.
    Matched MeSH terms: Carcinogens/analysis*
  8. Metal pollution in freshwater fish: A key indicator of contamination and carcinogenic risk to public health
    Panda BP, Mohanta YK, Parida SP, Pradhan A, Mohanta TK, Patowary K, et al.
    Environ Pollut, 2023 Aug 01;330:121796.
    PMID: 37169242 DOI: 10.1016/j.envpol.2023.121796
    Metals are micropollutants that cannot be degraded by microorganisms and are infiltrated into various environmental media, including both freshwater and marine water. Metals from polluted water are absorbed by many aquatic species, especially fish. Fish is a staple food in the diets of many regions in the world; hence, both the type and concentration of metals accumulated and transferred from contaminated water sources to fish must be determined and assessed. In this study, the heavy metal concentration was determined and assessed in fish collected from freshwater sources via published literature and Estimated Daily Intake (EDI), Target hazard quotient (THQ), and Carcinogenic Risk (CR) analyses, aiming to examine the metal pollution in freshwater fish. The fish was used as a bioindicator, and Geographic information system (GIS) was sued to map the polluted regions. The results confirmed that Pb was detected in fish sampled at 28 locations, Cr at 24 locations, Cu and Zn at 30 locations, with values Pb detected ranging from 0.0016 mg kg-1 to 44.3 mg kg-1, Cr detected ranging from 0.07 mg kg-1 to 27 mg kg-1, Cu detected ranging from 0.031 mg kg-1 to 35.54 mg kg-1, and Zn detected ranging from 0.242 mg kg-1 to 103.2 mg kg-1. The strongest positive associations were discovered between Cu-Zn (r = 0.74, p 
    Matched MeSH terms: Carcinogens/analysis
  9. Fulltext Liver Pathology in Rats Treated with Newcastle Disease Virus Strains AF2240 and V4-UPM
    Assayaghi RM, Alabsi AM, Swethadri G, Ali AM
    Asian Pac J Cancer Prev, 2019 Oct 01;20(10):3071-3075.
    PMID: 31653156 DOI: 10.31557/APJCP.2019.20.10.3071
    BACKGROUND: Treatment of cancer with chemo-radiotherapy causes severe side effects due to cytotoxic effects towards normal tissues which often results in morbidity. Therefore, developing anticancer agents which can selectively target the cancer cells and cause less side effects are the main objectives of the new therapeutic strategies for treatment advanced or metastatic cancers. Newcastle disease virus strains AF2240 and V4-UPM were shown to be cytolytic against various cancer cells in-vitro and very effective as antileukemicagents.

    METHODS: 45 rats at 6 weeks of age, were randomly assigned to nine groups with 5 rats in each group, both azoxymethane (AOM) and 5-Fluorouracil (5-FU) were given to rats according to the body weight. NDV virus strains (AF2240 and V4-UPM) doses were determined to rats according to CD50 resulted from MTT assay. After 8 doses of NDV strians and 5-FU, tissue sections preparations and histopathological study of rats' organs were done.

    RESULTS: In this article morphological changes of rats' organs, especially in livers, after treatment with a colon carcinogen (azoxymethane) and Newcastle disease virus strains have been recorded. We observed liver damage caused by AOM evidenced by morphological changes and enzymatic elevation were protected by the oncolytic viruses sections. Also we found that combination treatment NDV with 5-FU had greater antitumor efficacy than treatment with NDV or 5-FU alone.

    CONCLUSION: We noted morphological changes in liver and other rats' organs due to a chemical carcinogen and their protection by NDV AF2240 and NDV V4-UPM seems to be most protective.

    Matched MeSH terms: Carcinogens/toxicity
  10. Fulltext Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?
    Robey RB, Weisz J, Kuemmerle NB, Salzberg AC, Berg A, Brown DG, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1(Suppl 1):S203-31.
    PMID: 26106140 DOI: 10.1093/carcin/bgv037
    Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.
    Matched MeSH terms: Carcinogens, Environmental/adverse effects*
  11. Fulltext Disruptive chemicals, senescence and immortality
    Carnero A, Blanco-Aparicio C, Kondoh H, Lleonart ME, Martinez-Leal JF, Mondello C, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1(Suppl 1):S19-37.
    PMID: 26106138 DOI: 10.1093/carcin/bgv029
    Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.
    Matched MeSH terms: Carcinogens/administration & dosage*
  12. Simultaneous determination of multi-mycotoxins in palm kernel cake (PKC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS)
    Yibadatihan S, Jinap S, Mahyudin NA
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2014;31(12):2071-9.
    PMID: 25396715 DOI: 10.1080/19440049.2014.978396
    Palm kernel cake (PKC) is a useful source of protein and energy for livestock. Recently, it has been used as an ingredient in poultry feed. Mycotoxin contamination of PKC due to inappropriate handling during production and storage has increased public concern about economic losses and health risks for poultry and humans. This concern has accentuated the need for the evaluation of mycotoxins in PKC. Furthermore, a method for quantifying mycotoxins in PKC has so far not been established. The aims of this study were therefore (1) to develop a method for the simultaneous determination of mycotoxins in PKC and (2) to validate and verify the method. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using an electrospray ionisation interface (ESI) in both positive- and negative-ion modes was developed for the simultaneous determination of aflatoxins (AFB₁, AFB₂, AFG₁ and AFG₂), ochratoxin A (OTA), zearalenone (ZEA), deoxynivalenol (DON), fumonisins (FB₁ and FB₂), T-2 and HT-2 toxin in PKC. An optimum method using a 0.2 ml min⁻¹ flow rate, 0.2% formic acid in aqueous phase, 10% organic phase at the beginning and 90% organic phase at the end of the gradient was achieved. The extraction of mycotoxins was performed using a solvent mixture of acetonitrile-water-formic acid (79:20:1, v/v) without further clean-up. The mean recoveries of mycotoxins in spiked PKC samples ranged from 81% to 112%. Limits of detection (LODs) and limits of quantification (LOQs) for mycotoxin standards and PKC samples ranged from 0.02 to 17.5 μg kg⁻¹ and from 0.06 to 58.0 μg kg⁻¹, respectively. Finally, the newly developed method was successfully applied to PKC samples. The results illustrated the fact that the method is efficient and accurate for the simultaneous multi-mycotoxin determination in PKC, which can be ideal for routine analysis.
    Matched MeSH terms: Carcinogens, Environmental/analysis*; Carcinogens, Environmental/chemistry
  13. Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia
    Jahurul MH, Jinap S, Ang SJ, Abdul-Hamid A, Hajeb P, Lioe HN, et al.
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2010 Aug;27(8):1060-71.
    PMID: 20589547 DOI: 10.1080/19440041003801190
    The intake of heterocyclic amines is influenced by the amount and type of meat and fish ingested, frequency of consumption, cooking methods, cooking temperature, and duration of cooking. In this study, the dietary intake of heterocyclic amines in Malaysia and their main sources were investigated. Forty-two samples of meat and fish were analysed by high-performance liquid chromatography with photodiode array detector to determine the concentration of the six predominant heterocyclic amines, namely: 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f] quinoline(MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f] quinoxaline (7,8-DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Dietary intake data were obtained using a food-frequency questionnaire when interviewing 600 Malaysian respondents. The level of total heterocyclic amines in food samples studies ranged from not detected to 38.7 ng g(-1). The average daily intake level of heterocyclic amine was 553.7 ng per capita day(-1). The intake of PhIP was the highest, followed by MeIQx and MeIQ. The results reveal that fried and grilled chicken were the major dietary source of heterocyclic amines in Malaysia. However, the heterocyclic amine intake by the Malaysian population was lower than those reported from other regions.
    Matched MeSH terms: Carcinogens/administration & dosage*; Carcinogens/analysis; Carcinogens/isolation & purification
  14. Fulltext Chronic hepatitis B infection and liver cancer
    Wong Ch, Goh K
    Biomed Imaging Interv J, 2006 Jul;2(3):e7.
    PMID: 21614253 MyJurnal DOI: 10.2349/biij.2.3.e7
    Hepatitis B virus (HBV) is one of the most well recognised human carcinogens. Since its discovery about 40 years ago, HBV has been studied extensively. This article summarises the evidence derived from various studies including epidemiological, animal model, histopathology studies and molecular genetics studies leading to the establishment of HBV as the main aetiological agent for hepatocellular carcinoma (HCC). The reduction in the incidence of childhood HCC due to mass hepatitis B vaccination in Taiwan is a dramatic demonstration of the critical aetiological role of hepatitis B in HCC. Thus it is essential for interventionalists to understand the epidemiological and pathogenesis of HCC to ensure optimal patient care.
    Matched MeSH terms: Carcinogens
  15. Long-term tocotrienol supplementation and glutathione-dependent enzymes during hepatocarcinogenesis in the rat
    Rahmat A, Wan Ngah WZ, Gapor A, Khalid BA
    Asia Pac J Clin Nutr, 1993 Sep;2(3):129-34.
    PMID: 24352144
    The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethyl nitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by the determination of plasma and liver gamma-glutamyl transpeptidase (GGT), cytosolic glutathione reductase (GSSG-Rx), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). Twenty-eight male Rattus norwegicus rats (120-160g) were divided according to treatments into four groups: control group, tocotrienol - supplemented diet group (30mg/kg food), DEN/AAF-treated group and DEN/AAF treated plus tocotrienol-supplemented-diet group (30mg/kg food). The rats were sacrificed after nine months. The results obtained indicated no difference in the morphology and histology of the livers of control and tocotrienol-treated rats. Greyish-white neoplastic nodules (two per liver) were found in all the DEN/ AAF treated rats (n-10) whereas only one nodule was found in one of the carcinogen treated rats receiving tocotrienol supplementation (n-6). Histological examination showed obvious cellular damage for both the DEN/AAF-treated rats and the tocotrienol-supplemented rats but were less severe in the latter. Treatment with DEN/AAF caused increases in GGT, GSH-Px, GST and GSSG-Rx activities when compared to controls. These increases were also observed when tocotrienol was supplemented with DEN/AAF but the increases were less when compared to the rats receiving DEN/AAF only.
    Matched MeSH terms: Carcinogens
  16. Fulltext Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2
    Abdul Rahman M, Tan ML, Johnson SP, Hollows RJ, Chai WL, Mansell JP, et al.
    PeerJ, 2020;8:e10328.
    PMID: 33240646 DOI: 10.7717/peerj.10328
    Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease.
    Matched MeSH terms: Carcinogens
  17. Characterization and Risk Analysis of Metals Associated with Urban Dust in Rawang (Malaysia)
    Praveena SM
    Arch Environ Contam Toxicol, 2018 Oct;75(3):415-423.
    PMID: 29802419 DOI: 10.1007/s00244-018-0537-7
    This study was designed to determine the particle size distribution and develop road dust index combining source and transport factors involving road dust for dust pollution quantification in Rawang. Principal component analysis (PCA) was applied to identify possible sources of potentially toxic elements and spot major pollution areas in Rawang. The health risks (carcinogenic and noncarcinogenic) to adults and children were assessed using the hazard index and total lifetime cancer Risk, respectively. A total of 75 road dust samples were collected and particle sizes (1000, 500, 250, 160, 125 and 63 µm) were determined. Concentrations of potentially toxic elements (Cu, Cd, Co, Cr, Pb, Ni, Zn and As) in particle size of 63 µm were analyzed. The results demonstrated that the highest grain size of 250 µm has contributed almost more than 25% of atmospheric particulate pollution. The highest potentially toxic element concentration was Pb (593.3 mg/kg), whereas the lowest was Co (5.6 mg/kg). Road dust index output indicated that pollution risk fell into moderate levels in eastern and northern areas of Rawang. Similarly, PCA results revealed that potentially toxic elements (Cu, Cd, Pb, Zn, Ni and Cr) were linked with anthropogenic sources (urbanization process, industrial and commercial growth, urban traffic congestion) in northern and southern parts of Rawang. Cobalt and As concentrations were explained mainly from natural sources. Noncarcinogenic risk by hazard index value more than 1.0 was indicated for adults and children. Similarly, carcinogenic risk by total lifetime cancer risk value also showed carcinogenic risks among adults and children.
    Matched MeSH terms: Carcinogens
  18. Fulltext Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review
    Venkatachalam K, Vinayagam R, Arokia Vijaya Anand M, Isa NM, Ponnaiyan R
    Toxicol Res (Camb), 2020 Feb;9(1):2-18.
    PMID: 32440334 DOI: 10.1093/toxres/tfaa004
    1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.
    Matched MeSH terms: Carcinogens
  19. 3-Chloropropane-1,2-diol (3-MCPD) in Soy Sauce: A Review on the Formation, Reduction, and Detection of This Potential Carcinogen
    Lee BQ, Khor SM
    Compr Rev Food Sci Food Saf, 2015 Jan;14(1):48-66.
    PMID: 33401813 DOI: 10.1111/1541-4337.12120
    Soy sauce, a dark-colored seasoning, is added to enhance the sensory properties of foods. Soy sauce can be consumed as a condiment or added during the preparation of food. There are 3 types of soy sauce: fermented, acid-hydrolyzed vegetable protein (acid- HVP), and mixtures of these. 3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminants formed during the preparation of soy sauce and was found to be a by-product of acid-HVP-produced soy sauce in 1978. 3-MCPD has been reported to be carcinogenic, nephrotoxic, and reproductively toxic in laboratory animal testing and has been registered as a chemosterilant for rodent control. 3-MCPD is classified as a possible carcinogenic compound, and the maximum tolerated limit in food has been established at both national and international levels. The purpose of this review is to provide an overview on the detection of 3-MCPD in soy sauce, its toxic effects, and the potential methods to reduce its concentration, especially during the production of acid-HVP soy sauce. The methods of quantification are also critically reviewed with a focus on efficiency, suitability, and challenges encountered in analysis.
    Matched MeSH terms: Carcinogens
  20. Application of response surface methodology for the optimization of polycyclic aromatic hydrocarbons degradation from potable water using photo-Fenton oxidation process
    Abd Manan TSB, Khan T, Sivapalan S, Jusoh H, Sapari N, Sarwono A, et al.
    Sci Total Environ, 2019 May 15;665:196-212.
    PMID: 30772550 DOI: 10.1016/j.scitotenv.2019.02.060
    Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds, composed of benzene rings. The objective of this research was to identify the optimum condition for the degradation of PAHs contaminated water using photo-Fenton oxidation process via response surface methodology (RSM). Aqueous solution was prepared and potable water samples were collected from water treatment plants in Perak Tengah, Perak, Malaysia in September 2016. The reaction time, pH, molarity of H2O2 and FeSO4 were analyzed followed by RSM using aqueous solution. A five level central composite design with quadratic model was used to evaluate the effects and interactions of these parameters. The response variable was the percentage of total organic carbon (TOC) removal. PAHs quantification was done using gas chromatography mass spectrometry analysis. The regression line fitted well with the data with R2 value of 0.9757. The lack of fit test gives the highest value of Sum of Squares (15,666.64) with probability F value 0.0001 showing significant quadratic model. The optimum conditions were established corresponding to the percentage of TOC removal. The PAHs removal efficiency for potable water samples ranged from 76.4% to 91% following the first order of kinetic rates with R2 values of >0.95. Conventional water treatment techniques are not effective for PAHs removal. Thus, advanced oxidation processes may be considered as an alternative to conventional water treatment techniques in Malaysia and other developing countries.
    Matched MeSH terms: Carcinogens
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