This study aimed to estimate the Malaysian adult population's current dietary exposure and margin of exposure (MOE) to the carcinogenic processing contaminant, acrylamide. A total of 448 samples from 11 types of processed foods were collected randomly throughout Malaysia in the year 2015 and 2016. Acrylamide was analysed in samples using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) with a limit of detection (LOD) of 10 μg/kg and a limit of quantification (LOQ) of 25 μg/kg. The highest average level of acrylamide (772 ± 752 μg/kg) was found in potato crisps, followed by French fries (415 ± 914 μg/kg) and biscuits (245 ± 195 μg/kg). The total acrylamide exposure for the adult Malaysian was 0.229 and 1.77 μg/kg body weight per day for average and high consumers, respectively. The MOE were 741 and 1875 for the average consumer based on cancer and non-cancer effects of acrylamide, respectively. Meanwhile, for high consumers, the MOE is 96 for cancer and 243 for non-cancer effects. These findings indicate potential carcinogenic risks from acrylamide exposure among Malaysian adults, especially in Malay and other Bumiputra groups compared to Chinese, Indian, and other ethnic groups, while non-cancer effects appeared less concerning.
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
Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.
Rapid industrialization and urbanization have resulted in environmental pollution and unsustainable development of cities. The concentration of 12 potentially toxic metal(loid)s in windowsill dust samples (n = 50) were investigated from different functional areas of Qom city with the highest level of urbanization in Iran. Spatial analyses (ArcGIS 10.3) and multivariate statistics including Principal Component Analysis and Spearman correlation (using STATISTICA-V.12) were adopted to scrutinize the possible sources of pollution. The windowsill dust was very highly enriched with Sb (50 mg/kg) and Pb (1686 mg/kg). Modified degree of contamination (mCd) and the pollution load indices (PLIzone) indicate that windowsill dust in all functional areas was polluted in the order of industrial > commercial > residential > green space. Arsenic, Cd, Mo, Pb, Sb, Cu, and Zn were sourced from a mixture of traffic and industrial activities, while Mn in the dust mainly stemmed from mining activities. Non-carcinogenic health risk (HI) showed chronic exposure of Pb for children in the industrial zone (HI = 1.73). The estimations suggest the possible carcinogenic risk of As, Pb, and Cr in the dust. The findings of this study reveal poor environmental management of the city. Emergency plans should be developed to minimize the health risks of dust to residents.
Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P
Industrial effluents contain several organic and inorganic contaminants. Among others, dyes and heavy metals introduce a serious threat to drinking waterbodies. These pollutants can be noxious or carcinogenic in nature, and harmful to humans and different aquatic species. Therefore, it is of high importance to remove heavy metals and dyes to reduce their environmental toxicity. This has led to an extensive research for the development of novel materials and techniques for the removal of heavy metals and dyes. One route to the removal of these pollutants is the utilization of magnetic carbon nanotubes (CNT) as adsorbents. Magnetic carbon nanotubes hold remarkable properties such as surface-volume ratio, higher surface area, convenient separation methods, etc. The suitable characteristics of magnetic carbon nanotubes have led them to an extensive search for their utilization in water purification. Along with magnetic carbon nanotubes, the buckypaper (BP) membranes are also favorable due to their unique strength, high porosity, and adsorption capability. However, BP membranes are mostly used for salt removal from the aqueous phase and limited literature shows their applications for removal of heavy metals and dyes. This study focuses on the existence of heavy metal ions and dyes in the aquatic environment, and methods for their removal. Various fabrication approaches for the development of magnetic-CNTs and CNT-based BP membranes are also discussed. With the remarkable separation performance and ultra-high-water flux, magnetic-CNTs, and CNT-based BP membranes have a great potential to be the leading technologies for water treatment in future.
This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by hypersensitivity of the skin to ultraviolet radiation and other carcinogenic agents. This ailment is characterized by increased photosensitivity, skin xerosis, early skin aging, actinic keratosis, erythematous lesions, and hyperpigmentation macules. In this serial case report, we presented four cases with XP from two families in Indonesia. Both families were referred from rural referral health centers, and each family has two affected siblings. They had freckle-like pigmentation on the face, trunk, and extremities, which progressed since childhood. One patient of family 2 died because of an infectious disease. Histopathological examination using cytokeratine (CK), CD10, and Ber-EP4 staining from available tissue biopsy of one affected case of family 1 identified basal cell carcinoma (BCC) on the cheek and melanoma on the right eye. Mutation analysis found ERCC2, c2047C>T and XPC, c1941T>A in the first and second families, respectively. We suppose that this is the first case report of XP in Indonesia that incorporates clinical examination, genetic analysis, and extensive histopathological examination, including immunohistochemistry staining, and a novel pathogenic variant of XPC was found in the second family.
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.
Breast cancer is the most commonly diagnosed cancer among women and one of the leading causes of cancer mortality worldwide, in which the most severe form happens when it metastasizes to other regions of the body. Metastasis is responsible for most treatment failures in advanced breast cancer. Epithelial-mesenchymal transition (EMT) plays a significant role in promoting metastatic processes in breast cancer. MicroRNAs (miRNAs) are highly conserved endogenous short non-coding RNAs that play a role in regulating a broad range of biological processes, including cancer initiation and development, by functioning as tumor promoters or tumor suppressors. Expression of miR-548m has been found in various types of cancers, but the biological function and molecular mechanisms of miR-548m in cancers have not been fully studied. Here, we demonstrated the role of miR-548m in modulating EMT in the breast cancer cell lines MDA-MB-231 and MCF-7. Expression data for primary breast cancer obtained from NCBI GEO datasets showed that miR-548m expression was downregulated in breast cancer patients compared with healthy group. We hypothesize that miR-548m acts as a tumor suppressor in breast cancer. Overexpression of miR-548m in both cell lines increased E-cadherin expression and decreased the EMT-associated transcription factors SNAI1, SNAI2, ZEB1 and ZEB2, as well as MMP9 expression. Consequently, migration and invasion capabilities of both MDA-MB-231 and MCF-7 cells were significantly inhibited in miR-548m-overexpressing cells. Analysis of 1059 putative target genes of miR-548m revealed common pathways involving both tight junction and the mTOR signaling pathway, which has potential impacts on cell migration and invasion. Furthermore, this study identified aryl hydrocarbon receptor (AHR) as a direct target of miR-548m in breast cancer cells. Taken together, our findings suggest a novel function of miR-548m in reversing the EMT of breast cancer by reducing their migratory and invasive potentials, at least in part via targeting AHR expression.
Food contamination is a serious concern because of a high level of chemicals in food causes severe health issues. Safeguarding the public from the risk of adulterated foods has become a challenging mission. Chloropropanols are of importance to food safety and food security because they are common chemical food contaminants and believed to be carcinogenic to humans. In chemical sensing, chloropropanols are challenging analytes owing to the lacking diversity of functional groups and difficulty in targeting the hydroxyl group in aqueous environments. Moreover, because of their small molecular size, the compositions of chloropropanols remain challenging for achieving chromatographic determination. Herein, to simulate human smell and taste sensations, serum albumins, which are protein-based receptors, were introduced as low-selective receptors for differential sensing. Utilizing serum albumins, a fluorophore (PRODAN), and an additive (ascorbic acid), a differential-based optical biosensor array was developed to detect and differentiate chloropropanols. By integrating the sensor array with linear discriminant analysis (LDA), four chloropropanols were effectively differentiated based on their isomerism properties and the number of the hydroxyl groups, even at ultra-low concentration (5 nM). This concentration is far below the maximum tolerable level of 0.18 μM for chloropropanols. The sensing array was then employed for chloropropanols differentiation and quantification in the complex mixtures (e.g., synthetic soy and dark soy sauces). Leave-one-out cross-validation (LOOCV) analysis demonstrated 100% accurate classification for all tests. These results signify our differential sensing array as a practical and powerful tool to speedily identify, differentiate, and even quantify chloropropanols in food matrices.
3-Monochloropropane-1,2-diol (3-MCPD) esters and glycidyl esters (GE) are heat-induced contaminants which form during oil refining process, particularly at the high temperature deodorization stage. It is worth to investigate the content of 3-MCPD and GE in fries which also involved high temperature. The content of 3-MCPD esters and GE were monitored in fries. The factors that been chosen were temperature and duration of frying, and different concentration of salt (NaCl). The results in our study showed that the effect was in the order of concentration of sodium chloride
Heterocyclic amines (HCAs) are carcinogenic food toxicants formed in cooked meats, which may increase the risk of cancer development in humans. Therefore, in this study, the effect of stingless bee honey from different botanical origins on the formation of HCAs in grilled beef satay was investigated. HCAs concentration in grilled beef satay was determined by using high performance liquid chromatography (HPLC). In total, six of the most toxigenic HCAs representing aminoimidazo-azaarenes (AIAs) (MeIQx, 4,8-DiMeIQx, and PhIP) and amino carbolines (norharman, harman, and AαC) groups were identified in all the beef samples investigated. A significant reduction in HCAs was observed in grilled beef marinated in honey as compared to beef samples marinated in table sugar (control), in which the reduction of 95.14%, 88.45%, 85.65%, and 57.22% was observed in gelam, starfruit, acacia, and Apis honey marinades, respectively. According to the partial least squares regression (PLS) model, the inhibition of HCAs in grilled beef was shown to be significantly correlated to the antioxidant activity (IC50) of the honey samples. Therefore, the results of this study revealed that the addition of stingless bee honey could play an important role in reducing HCAs in grilled beef.
We developed an innovative single-step pyrolysis approach that combines microwave heating and activation by CO2 or steam to transform orange peel waste (OPW) into microwave activated biochar (MAB). This involves carbonization and activation simultaneously under an inert environment. Using CO2 demonstrates dual functions in this approach, acting as purging gas to provide an inert environment for pyrolysis while activating highly porous MAB. This approach demonstrates rapid heating rate (15-120 °C/min), higher temperature (> 800 °C) and shorter process time (15 min) compared to conventional method using furnace (> 1 h). The MAB shows higher mass yield (31-44 wt %), high content of fixed carbon (58.6-61.2 wt %), Brunauer Emmett Teller (BET) surface area (158.5-305.1 m2/g), low ratio of H/C (0.3) and O/C (0.2). Activation with CO2 produces more micropores than using steam that generates more mesopores. Steam-activated MAB records a higher adsorption efficiency (136 mg/g) compared to CO2 activation (91 mg/g), achieving 89-93 % removal of Congo Red dye. The microwave pyrolysis coupled with steam or CO2 activation thereby represents a promising approach to transform fruit-peel waste to microwave-activated biochar that remove hazardous dye.
Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.
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.
Chemical carcinogens are commonly used to investigate the biology and prognoses of various cancers. This study investigated the mechanism of leukaemogenic effects of n-ethyl-n-nitrosourea (ENU) in a mouse model. A total of 14 3-week-old male Institute of Cancer Research (ICR)-mice were used for the study. The mice were divided into groups A and B with seven mice each. Group A served as the control while group B received intraperitoneal (IP) injections of 80 mg/kg ENU twice with a one-week interval and were monitored monthly for 3 months for the development of leukaemia via blood smear examination. The mice were sacrificed humanely using a CO2 chamber. Blood, spleen, lymph nodes, liver, kidney and lung samples were collected for blood smear examination and histopathological evaluation. The expression of angiogenic protein (VEGF), and pro and anti-apoptotic proteins (BCL2 and BAX), was detected and quantified using Western blot technique. Leukaemia was confirmed by the presence of numerous blast cells in the peripheral blood smear in group B. Similarly, the VEGF and BCL2 proteins were significantly (p < 0.05) upregulated in group B compared to A. It is concluded that IP administration of 80 mg/kg ENU induced leukaemia in ICR-mice 12 weeks post administration through upregulation of angiogenic and anti-apoptotic proteins: VEGF and BCL2.
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.
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.
Malaysia is the world’s third largest exporter of liquified natural gas and the second largest oil and natural gas producer in Southeast Asia, following Indonesia. The potential air pollutants released from the industry may affect the health of the population. The primary objective of this study was to determine the potential health risk among the population in the zone of impact. This was a comparative case study between controlled and uncontrolled emissions based on the air dispersion modelling. Hazard quotient (HQ) was used to assess non-carcinogenic risk, while lifetime cancer risk (LCR) was used to assess carcinogenic risk. All ambient air pollutant levels were within permissible levels and adhered to the standard. The HQ for hydrogen sulphide and benzene was less than one in all scenarios. The LCR for benzene was acceptable in all scenarios. Advanced pollution prevention equipment should be installed within the gas emission system to treat the final emission to meet prescribed permissible limits. Continuous ambient air monitoring and effective control measures should be practiced to ensure the sustainability of clean air. The health risk assessment showed no risk of developing malignancy and non-cancer disorder among the workers and general population living surround the petrochemical plants. This allows the development of the petroleum refinery plants to be continued.