Human activities in a large array of industrial and agricultural sectors produce chemical contaminants which are chiefly hydrocarbons of various types that are potentially toxic and carcinogenic to aquatic and terrestrial organisms. Globally, millions of tons of these pollutants are generated annually, and in some areas, they are released indiscriminately to the environment. In order to overcome this problem, microbiological decontamination or bioremediation has been suggested. Bioremediation has been argued to be an efficient, economic, and adaptable alternative to physicochemical remediation. However, to date, such claims of successful bioremediation are often not supported by evidence from toxicity studies. In this regard, luminescent bacteria have been employed in some hydrocarbon remediation experiments to denote reduction in toxicity. In this review, the utilization of luminescence bacteria as toxicity monitoring agent for hydrocarbon remediation is discussed.
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.
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.
Talc’s softness, whiteness, lamellarity, inertness and affinity for organic chemicals make it valuable for industrial and domestic applications. The largest consumers are the paper and ceramic industry; only 5% is used as cosmetics. It is also used for preserving animal feed, and a carrier for drugs, insecticides, pesticides and chemicals. Talc was introduced as baby powder in 1894 and advertised aggressively worldwide. Widespread and indiscriminate use soon raised concerns about its implications for health. The IARC found that talc containing asbestiform fibres is carcinogenic to humans, but inadequate evidence to implicate talc not-containing asbestiform fibres. Pulmonary manifestations of talc inhalation include talcosis, talcosilicosis, and talcoasbestosis. Drug-users administering talc-adulterated oral medications intravenously develop pulmonary granulomas, fibrosis and irreversible pulmonary hypertension. Worldwide reports reveal talc inhalation is fatal to infants; it coats and dries mucus membranes, causes hemorrhage, edema, desquamation of bronchial epithelium, and clogs and compromises mucociliary clearance; larger quantities completely obstruct airways. Progressive diffuse pulmonary fibrosis is a recognized sequel to massive aspiration of baby powder. IARC has classified perineal use of talcum powder as a possible ovarian carcinogen, while a recent study has found that perineal talcum powder increases the risk of endometrial cancer among postmenopausal women. There is a need to raise public awareness of the serious risks associated with the use of talcum powder and for legislation to protect the health of the uninformed who represent the poorer segment of the community, and infants and young children. The dangers associated with cosmetic use of talc outweigh any possible benefits.
Rat large intestine is an established model to study the effect of
carcinogens. There are several distinctive features among mammalian gastrointestinal
tracts in gross anatomy but they share some basic similar structures. The variety in
digestive system relies on its physiology. Rats rarely eat high fatty diets, thus the
function of gall bladder become less significant in their digestive system and this is
justified by the fact that rats have none. Rats have large caecum designated for their
fermentation chamber to digest cellulose. Another notable difference is the size and
length of colon itself, in which human colon is significantly bigger and longer. We aimed
to demonstrate the gross anatomy and histology of rat digestive system particularly the
large intestine. (Copied from article).
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.
Unprocessed ‘budu’ is a mixture of anchovies and salt that has been fermented for a period of time, and has not been heat-treated nor formulated with additional ingredients. This study analyzed Malaysian
unprocessed ‘budu’ from 12 producers for microbiological, salt, protein, histamine and 3-MCPD contents.
The results demonstrated that Malaysian unprocessed ‘budu’ were free from pathogenic Coliform, E. coli,
V. parahaemolyticus and V. cholerae contaminations. Carcinogenic 3-MCPD was below detection level of 2 ppb for all 12 samples tested. However, 58% of the unprocessed ‘budu’ had histamine content greater than the hazardous levels of 50 mg/100 g sample.
Roasting is an important process that contribute to formation of flavour compounds in cocoa beans. Pyrazines, a by-product of Maillard reaction is one of the character impact compounds that contribute to unique cocoa flavour. Unfortunately during roasting, carcinogenic acrylamide are also produced through Maillard reaction. Therefore, this study was focussed on optimising the roasting conditions using Central Composite Design (CCD) to produce superior quality cocoa beans with high concentration of pyrazines and low concentration of acrylamide. The roasting conditions used were temperatures in the range of 110⁰C to 160⁰C and time ranging from 15 min to 40 min. Roasting conditions significantly (p
The aim of this study is to determine the antioxidant capacity of underutilized fruits in Malaysia namely Milk apple (Syzygium malaccense), Malay apple (Syzygium malaccense (L.) Merr. and Perry), and Water apple (Syzygium aqueum). Synthetic antioxidants (BHA and BHT) commonly used in the food industries may not be as safe as it was presumed earlier. As BHA and BHT may be carcinogenic, it is important to look for new sources of natural antioxidants from fruits and vegetables. Freeze dried samples extracted with acetone and water were measured by ferric 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and Ferric Reducing Antioxidant Power (FRAP) assays. Acetone extract (50%) showed higher values for both DPPH and FRAP assays compared with water extract. Milk apple has the highest DPPH value of 95.26% inhibition of DPPH. Milk apple also showed the highest FRAP value with 8722.22 µM of Fe (II) per gram of freeze dried sample. There was a significant difference (P < 0.05) in the types of extraction used. Antioxidant capacities of the samples are in the following order: Milk apple > Malay apple > Water apple. Proximate compositions and mineral contents of the samples were determined too. The samples can be used as a source of natural antioxidants.
Early studies reported that a styrylpyrone derivative (SPD) purified from the Goniothalamus sp. acts as a non-competitive antiestrogen in early pregnant mice (1). In the immature rat uterine wet weight test, we found that SPD markedly reduced uterine weight at doses 1 and 100 mg/kg, thus reflecting negative antiestrogenicity, probably attributed to low binding affinities towards ER. Tamoxifen (Tam) on the other hand exhibited partial antiestrogenicity at all doses (0.01-10 mg/kg BW) and dose-dependent estrogenicity. However, the estrogen antagonism: agonism ratio for SPD is much higher than Tam, which is indicative of the breast cancer antitumor activity as seen in compounds such as MER-25. Pretreatment assessment on 1 mg/kg BW SPD and Tam showed that SPD is not a very good, estrogen antagonist compared to Tam, as it was unable to revert the estrogenicity effect of estradiol benzoate (EB) on immature rat uterine weight. Antitumor activity assessment for SPD exhibited significant tumor growth retardation in 7,12-dimethyl benzanthracene (DMBA) induced rat mammary tumors at all doses employed (2, 10 and 50 mg/kg) compared to the controls (p < 0.01). This compound was found to be more potent than Tam (2 and 10 mg/kg) and displayed greater potency at a dose of 10 mg/kg. It caused complete remission of 33.3% of tumors but failed to prevent onset of new tumors. However, SPD administration at 2 mg/kg caused 16.7% complete remission and partial remission. It also prevented the onset of new tumors throughout the experiment.
Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.
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.
Colorants contained in palm oil mill effluent (POME) are recalcitrant and carcinogenic in nature. The commonly applied ponding treatment methods have been reported inefficient for remediating the concentration of the colorants before discharge. The need for sustainable and efficient treatment technique is crucial in order to preserve the environment. In this view, this study reported the first attempt to decolorize POME using a proliferate Klebsiella Pneumonia ABZ11 at varied inoculum sizes of 5-25% (v/v), initial color concentration (650-2,600 ADMI) and treatment time of 5-40 h. The treatment conditions were optimized using Response Surface Methodology. At optimal conditions of 20% (v/v) inoculum size, initial-color concentration of 2,600 ADMI, initial pH of 7 and 35 h treatment retention time, over 80.40% color removal was achieved with insignificant disparity compared with the model predicted value of 81.538%. Also, the Monod model excellently described the decolorization kinetic process with 0.9214 coefficient of correlation (R2), and the calculated maximum growth μ max ) and half-saturation constant (K s ) were 7.023 d-1 and 340.569 ADMI d-1, respectively. This study revealed that the Klebsiella Pneumonia ABZ11 was highly prolific and such feature may favor a synergistic biodegradation process.
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.
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.
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.
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.
The effect of 18 different chemicals, which included acidic compounds (sulfuric acid, chloridric acid, phosphoric acid, benzoic acid, citric acid, acetic acid), alkaline compounds (ammonia, sodium bicarbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide), salts (acetate ammonium, sodium bisulfite, sodium hydrosulfite, sodium chloride, sodium sulfate) and oxidising agents (hydrogen peroxide, sodium hypochlorite), on the reduction of aflatoxins B(1), B(2), G(1) and G(2) and ochratoxin A (OTA) was investigated in black and white pepper. OTA and aflatoxins were determined using HPLC after immunoaffinity column clean-up. Almost all of the applied chemicals showed a significant degree of reduction on mycotoxins (p < 0.05). The lowest and highest reduction of aflatoxin B(1), which is the most dangerous aflatoxin, was 20.5% ± 2.7% using benzoic acid and 54.5% ± 2.7% using sodium hydroxide. There was no significant difference between black and white peppers (p < 0.05).
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.
Cervical cancer is the most common gynecological cancer and one of the major causes of female cancer-related death worldwide particularly in developing countries. Thus far, there are a few in vivo models have been developed in investigating this type of cancer. In this study, we induced cervical cancer in Balb/c mice by exploiting the carcinogenic property of diestylstilbestrol (DES). The Balb/c pregnant mice were given subcutaneous (SC) injection of 67μg/kg body weight of DES on GD 13, and the mice gave birth approximately at gestation day 19-22. Female offspring were reared and the body weight was recorded once weekly. The female offspring were sacrificed at age of 5 months. Upon termination, blood was collected in a plain tube via cardiac puncture and the reproductive tracts were collected and weighed. The reproductive tract sections were stained using H&E for observation of pathological changes. The progression of disease state was monitored by measuring the level of serum interleukin (IL-6) using the Mouse IL-6 ELISA Assay Kit (BD OptEIA™, USA). All parameters were compared with Not-induced group. The outcome of this study demonstrated a significant difference in body weight gain, reproductive organ weight, diameter of cervix and the level of serum IL-6 in the Induced group as compared to the Not-induced group (P<0.05). Histopathological findings revealed the presence of adenosis only in the Induced group. It shows that DES could be employed as an agent to induce cervical carcinogenesis in animal model. In addition to that, new potential anti-cancer agents from various sources could be further evaluated using this technique.