Carcinogenic Research Articles

Ecological implications of chromium-contaminated effluents from Indian tanneries and their phytoremediation: a sustainable approach.

Industrial activities are paramount to sustaining the economy in a rapidly developing nation and global powerhouse like India. Leather industries are important in the country's economic map due to the high revenue and employment generation opportunities. Several of these industries contribute largely to environmental pollution. The pollution of the environment is mainly caused by improper disposal of the tannery effluents that are highly rich in hexavalent chromium, a potent human carcinogen. Hexavalent chromium imparts toxic effects on the biotic components, which include plants, animals, and humans. The review portrays the current status of the Indian leather tanning sector and its impact on the Indian economy. The process of chromium tanning and its adverse effects on the environmental biotic components have been briefly discussed. Phytoremediation of these effluents using suitable hyperaccumulating plants has been suggested as an eco-friendly and cost-effective approach for the sustainable restoration of the polluted environment. The mechanism behind the remediation approach and the factors influencing it have been detailed. The manuscript briefly discusses some important advancements in the field of phytoremediation and emerging technologies and concludes by emphasizing further research for sustainable management of tannery wastes.

Label-free detection of formaldehyde in water by titanium doped MoS2 gold nanoislands LSPR sensor

Formaldehyde is a known human carcinogen widely present in various industrial processes. Dissolved formaldehyde in water poses a significant threat to human health, not solely gases. Here, a novel label-free detection scheme of formaldehyde in aqueous environment via Ti-doped MoS2 as the functionalized layer on a localized surface plasmon resonance (LSPR) sensor is reported. It has been found that the strong adsorption of formaldehyde on Ti-doped MoS2 attached on gold nanoislands induces a strong local refractive index change and enables sensitive detection. Besides, the characterization and LSPR experimental results also highlight the contribution of the nanoislands morphology to facilitate improved surface attachment of Ti-doped MoS2, and in turn improves the sensing performance. Along with experimental work, density functional theory (DFT) calculation has shown the strong formaldehyde adsorption on Ti-doped MoS2 with water molecules included, therefore confirming its feasibility and effectiveness for sensing. The sensor has successfully achieved an excellent detection limit of 0.104 ppb with its selectivity studied and confirmed using DFT calculations and experiment. The practical value of this research lies in its potential development of this light-based sensor for water quality monitoring with the major advantages of facile synthesis, fast detection, and label-free sensing offered by LSPR.

Characterization of Molecular Subtypes of Rat Mammary Cancer and Their Association With Environmental Exposures.

Breast cancer is a heterogeneous disease with many subtypes, and the association between these subtypes and exposure to environmental factors such as radiation remains controversial. Although the rat is used widely for research into human breast cancer, the heterogeneity and subtype definitions are unclear. Here, we leveraged an archive of rat mammary cancer samples and gene expression microarray data to classify tumors and examine their association with exposures. Eighty-four mammary cancer and 12 normal mammary tissue samples were obtained from previous experiments in which rats were exposed to different types of radiation, chemical carcinogens, and diets. Tumors were then subjected to immunohistochemical (IHC) analysis of conventional biomarkers, as well as gene expression profiling; they were then classified by three approaches based on IHC results, the PAM50 classifier algorithm, and unsupervised clustering of gene expression profiles. IHC identified four subtypes (luminal A-like, luminal B-like 1, luminal B-like 2, and triple-negative), while PAM50 identified six (luminal A, luminal B, basal-like, HER2-enriched, normal-like, and claudin-low). Unsupervised clustering divided the tumors into three large, statistically significant, groups (named "luminal A", "luminal B", and "non-luminal" clusters). The results of the three approaches were significantly associated with each other. Exposure to radiation and chemical carcinogens during post-pubertal development was significantly associated with an increased risk of developing luminal A tumors, whereas exposure to a high corn-oil diet was associated with a higher likelihood of luminal B tumors. Rat mammary cancer subtypes resemble those in humans and are related to environmental factors.

Differential Selectivity of Human and Mouse ABCC4/Abcc4 for Arsenic Metabolites.

Millions of people globally are exposed to the proven human carcinogen arsenic at unacceptable levels in drinking water. In contrast, arsenic is a poor rodent carcinogen, requiring >100-fold higher doses for tumour induction, which may be explained by toxicokinetic differences between humans and mice. The human ATP-binding cassette (ABC) transporter hABCC4 mediates the cellular efflux of a diverse array of metabolites, including the GSH conjugate of the highly toxic monomethylarsonous acid (MMAIII), MMA(GS)2, and the major human urinary arsenic metabolite dimethylarsinic acid (DMAV). Our objective was to determine if mouse Abcc4 (mAbcc4) protected against and/or transported the same arsenic species as hABCC4. The anti-ABCC4 antibody M4I-10 epitope was first mapped to an octapeptide (411HVQDFTA418F) present in both hABCC4 and mAbcc4, enabling quantification of relative amounts of hABCC4/mAbcc4. mAbcc4 expressed in HEK293 cells did not protect against any of the six arsenic species tested [arsenite, arsenate, MMAIII, monomethylarsonic acid, dimethylarsinous acid or DMAV], despite displaying remarkable resistance against the antimetabolite 6-mercaptopurine (>9-fold higher than hABCC4). Furthermore, mAbcc4-enriched membrane vesicles prepared from transfected HEK293 cells did not transport MMA(GS)2 or DMAV, despite a >3-fold higher transport activity than hABCC4-enriched vesicles for the prototypic substrate 17β-estradiol-17-(β-D-glucuronide). Abcc4(+/+) mouse embryonic fibroblasts (MEFs) were ~3-fold more resistant to arsenate than Abcc4(-/-) MEFs; however, further characterization indicated this was not mAbcc4 mediated. Thus, under the conditions tested, arsenicals are not transported by mAbcc4, and differences between the substrate selectivity of hABCC4 and mAbcc4 seem likely to contribute to differences in human and mouse arsenic toxicokinetics. Significance Statement Toxicokinetics of the carcinogen arsenic differ among animal species. Arsenic methylation is known to contribute to this, whereas arsenic transporters have not been considered. The human ATP-binding cassette transporter hABCC4 is a high affinity transporter of toxicologically important arsenic metabolites. Here we used multiple cell models to demonstrate that mouse Abcc4 does not protect cells against, or transport, any arsenic species tested. Thus, differences between hABCC4 and mAbcc4 substrate selectivity likely contribute to differences in human and mouse arsenic toxicokinetics.

Low Magnetic Field Exposure Alters Prostate Cancer Cell Properties.

Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies.

Overview of human health effects related to glyphosate exposure.

Glyphosate is a chemical compound derived from glycine, marketed as a broad-spectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers' urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%-80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system.

Integrated evaluation of workplace exposures and biomarkers of bladder cancer among textile dyeing workers

BackgroundThe textile industry is the second risk factor for bladder cancer, after smoking. Previous studies focused on the impact of exposure to high concentrations of bladder carcinogenic chemicals in the textile dyeing industry on the elevation of bladder cancer biomarkers. This study aimed to evaluate bladder carcinogenic air pollutants in a textile dyeing factory and investigate its role and the role of serum 25-hydroxyvitamin D (25-OH vit. D) on cancer bladder biomarkers in exposed workers.MethodsA cross-sectional study was conducted. Particulate and vapor forms of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) were monitored in the printing, dyeing, and preparing sections of a textile factory. Bladder tumor antigen (BTA), nuclear matrix protein 22 (NMP-22), and 25-OH vit. D were estimated in all the exposed workers (147 exposed workers) and in workers not occupationally exposed to chemicals (130 unexposed workers).ResultsAromatic bladder carcinogenic compounds were either in low concentrations or not detected in the air samples of working areas. BTA and NMP-22 of exposed workers were not significantly different from the unexposed. However, 25-OH vit. D was significantly lower in the exposed than unexposed workers. There was a significant inverse correlation between 25-OH vit. D and duration of exposure in exposed workers.ConclusionThe mean levels of PAHs and VOCs were within the safe standard levels in the working areas. The non-significant difference in BTA and NMP-22 between the exposed and unexposed groups suggests the presence of occupational exposures to safe levels of bladder carcinogenic aromatics, while the significantly lower 25-OH vit. D levels among the exposed than the unexposed groups could suggest the potential association of 25-OH vit. D with occupational exposures to low levels of PAHs and VOCs, and this association was found to be inversely correlated with the duration of exposures. Accordingly, more specific predictor tests must be applied for early diagnosis of bladder cancer among the exposed workers.

Uncoupling as initiating event in mitochondrial dysfunction after diuron exposure

Diuron, a herbicide derived from urea, has been shown to induce urinary bladder urothelial tumors in rodents, leading the U.S. Environmental Protection Agency (USEPA) to designate it as a ‘known/likely’ human carcinogen. In our laboratory, a series of studies investigating the carcinogenic mode of action (MoA) of Diuron have consistently revealed its cytotoxic effects on the urinary bladder urothelium. Prolonged exposure to relatively high doses of Diuron results in urothelial necrosis, regenerative hyperplasia, and eventually, the development of tumors. The hypothesis posited is that Diuron and its metabolites exert toxicity by causing damage to mitochondria, a phenomenon referred to as mitotoxicity. Our research focuses on evaluating how Diuron and its metabolites affect mitochondria isolated from both the urothelium and the liver, the primary organ for Diuron biotransformation. In this context, we present and discuss data pertaining to mitochondria isolated from the liver of Wistar rats exposed to Diuron or its metabolites 3-(3,4-diclorofenil)-1-metilureia (DCPMU) or 3,4-dichloroaniline (DCA) at concentrations ranging from 0.5 to 500 µM in vitro. The findings indicate that, at concentrations of 100 and 500 µM, the tested chemicals induce uncoupling of oxidative phosphorylation, as evidenced by the dissipation of mitochondrial membrane potential and basal oxygen consumption. Notably, at 500 µM, DCA causes mitochondrial swelling, a morphofunctional indicator of severe organelle damage. These outcomes underscore the classification of Diuron and its metabolites, DCA and DCPMU, as mitotoxic to liver cells, given the pronounced mitochondrial dysfunction they induce.

Monoubiquitinated H2B, a Main Chromatin Target of Formaldehyde, Is Important for S-Phase Checkpoint Signaling and Genome Stability.

Formaldehyde (FA) is a human carcinogen with ubiquitous environmental exposures and significant endogenous formation. Genotoxic activity of FA stems from its reactivity with DNA-NH2 groups. Histone lysines are another source of aldehyde-reactive amino groups in chromatin, however, chromatin/histone damage responses to FA and their biological significance are poorly understood. We examined histone posttranslational modifications in FA-treated human lung cells and found that the majority of the most prominent small lysine modifications associated with active or inactive chromatin were unchanged. FA moderately decreased H3K9 and H3K27 acetylation and H2A-K119 monoubiquitination but caused surprisingly severe losses of H2B-K120 monoubiquitination, especially in primary and stem-like cells. H2Aub1 decreases reflected its slower ubiquitination linked to a lower ubiquitin availability due to K48-polyubiquitination of FA-damaged proteins. Depletion of H2Bub1 resulted from its rapid deubiquitination in part by ATXN7L3-associated deubiquitinases and was independent on DNA damage signaling, indicating a direct chromatin damage response. Manipulations of H2Bub1 abundance showed that it was important for robust ATM and ATR signaling, efficient S-phase checkpoint, and suppression of mitotic transmission of unreplicated DNA and formation of micronuclei. Our findings identified H2B deubiquitination as a major FA-induced chromatin damage response that regulates S-phase checkpoint signaling and genome stability.

Determination of free formaldehyde in cosmetics products through derivatization with 2,4-DNPH using an optimized and validated HPLC-PDA method

AbstractFormaldehyde plays a significant role in the global economy due to its unique chemical properties and widespread use in both the medical field and various industrial sectors. However, formaldehyde (HCHO) is classified as a persistent organic pollutant and is known to be harmful. Exposure to formaldehyde, both direct and prolonged, can cause severe health issues and potentially lead to death. It is recognized as a human carcinogen by numerous organizations and can negatively impact the endocrine system, as well as having mutagenic or teratogenic effects. Formaldehyde has been detected in various matrices at levels exceeding those permitted by international health regulatory bodies. Chromatography, particularly high-performance liquid chromatography (HPLC) coupled with detection methods, is an analytical technique frequently used to determine volatile organic molecules, including formaldehyde. This investigation aimed to develop and validate an assay method to identify and quantify formaldehyde in cosmetic products using HPLC-PDA. The chosen isocratic system consisted of a ZORBAX RX-C8 column (250 mm × 4.6 mm; 5 μm) and a mobile phase mixture of acetonitrile and water in a 55:45 (v/v) ratio, with a flow rate of 1.5 mL min−1. Formaldehyde was detected at 353 nm after derivatization with a 0.1N 2,4-dinitrophenylhydrazine solution, with a retention time of approximately 5.0 min and a total run time of 7.0 min for formaldehyde. The method was validated according to ICH Q2 (R1) guidelines. The validation parameters demonstrated high selectivity, precision (RSD <2%), accuracy (mean recovery of 101.3%), linearity (r > 0.995 in the 1,000–2,400 ppm range), and a limit of quantification (LOQ) of 0.1 ppm. The validated analytical method was applied to 35 cosmetic products. None of these products were labeled as containing formaldehyde, although 6 imported products were labeled as containing formaldehyde-releasing preservatives. The results indicated that 88.6% of the samples tested positive for formaldehyde, with free formaldehyde levels ranging from 20 to 981 ppm. All samples contained formaldehyde levels below the 2000 ppm threshold.

Carcinogenic risk to the health of the population of a large industrial city as a result of multi-environmental and multi-route exposure to chemicals

Introduction. Despite the relatively low average annual mortality rate, the increased incidence of cancer in the population of the Omsk region, together with indicators of the quality of oncological care, indicate a tense epidemiological situation. The purpose of the study is to determine priority environments and routes of exposure to chemicals in the formation of long-term carcinogenic risks in the city of Omsk. Materials and methods. There were used results of environmental and social-hygienic monitoring of habitat objects for the period 2017–2022. To assess the cumulative carcinogenic risk, atmospheric air, drinking tap water, open water, soil, food products, and 3 routes of exposure were taken into account: inhalation, oral and cutaneous. The assessment of carcinogenic risks was carried out in accordance with Guideline R 2.1.10.3968–23, taking into account the severity coefficient of malignant neoplasms. Results. The carcinogenic risk to the health of the population of the city of Omsk as a result of multi–environmenal and multi-route exposure to chemicals was assessed as alarming (high in an the engraved script). The structure of contributions to the cumulative carcinogenic risk: drinking water – 63.3%, atmospheric air – 33.1%, food products – 3.3 %, other environments less than 0.5%. The main route of entry of chemical carcinogens is inhalation (77.4%). Alarming carcinogenic risks were formed through the inhalation route of chloroform from drinking water; chromium VI, formaldehyde, benzene, and soot from atmospheric air. Among the target organs of malignant neoplasms, the greatest risk was in the gastrointestinal tract, which was assessed as alarming. Limitations. Not all habitat objects were analyzed, which may reduce the objectivity of the conclusions. Conclusion. An assessment of the long-term cumulative carcinogenic risk made it possible to prioritize the list of chemical pollutants, environmental objects, and routes of exposure to carcinogens. For more accurate planning of sanitary and hygienic measures to reduce public health risks, improve comprehensive monitoring of pollutants in all environments, taking into account all routes of entry into the human body, it is advisable to analyze the total risks for multi-environmental and multi-route exposure with an analysis of the contribution of chemicals, media, routes to their formation.

The food-borne carcinogenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) disrupts circadian rhythms and ameliorated by pterostilbene (PSB) in Caenorhabditis elegans.

The food-borne 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potential human carcinogen abundant in cooked meat. While circadian rhythms are crucial biological oscillations, the negative impact of PhIP on circadian systems and the potential of mitigation remain underexplored. We investigated the effects of PhIP on circadian rhythms and the mitigating effects of the phytochemical antioxidant pterostilbene (PSB) in Caenorhabditis elegans. We show that exposure to 10μM PhIP disrupts the 24-h circadian rhythms of C. elegans, an effect mitigated by co-exposure to 100μM PSB. In addition, PhIP-induced circadian disruption can be linked to defective oxidative stress resistance, which is associated with the DAF-16/FOXO pathway and is modulated by PSB. Molecular docking suggested that PhIP and PSB bind similarly to DAF-16. Moreover, 10μM PhIP abolished the rhythmic expression of the core clock gene prdx-2, which is restored by 100μM PSB. Findings from this study provide novel insight of how food-borne contaminant like PhIP may contribute to the disruption of circadian rhythms and suggest potential for PSB to mitigate these effects in higher organisms.

Teaching Strategies to Enhance Knowledge and Understanding of Opisthorchis viverrini and Cholangiocarcinoma in Thailand: Lessons for Asian Countries.

Although Opisthorchis viverrini (OV) is a neglected tropical disease, the International Agency for Research on Cancer (IARC) listed it as a human carcinogen 30years ago. Cholangiocarcinoma (CCA) is the ultimate pathology outcome. However, it remains a significant public health problem in the Greater Mekong Subregion and Asia. Its widespread impact on human health requires urgent action using various strategies. This study aimed to investigate and prioritize the need for developing teaching and learning management of OV and CCA among primary school students in Thailand endemic areas. The samples consisted of 36 Grade 6 students. This study was conducted by using a needs questionnaire. Data were analyzed using Mean and Standard Deviation. The needs were prioritized using the Modified Priority Needs Index (PNI modified). The findings revealed a moderate overall need for teaching and learning management development. The area with the highest need was learning activity organization (PNI = 0.410), followed by audiovisual equipment (PNI = 0.276) and buildings (PNI = 0.265). The teaching content the students needed most included CCA prevention, risk factors, and disease symptoms (58.33%). Based on the findings, it is suggested that teachers design various learning activities and emphasize hands-on activities for students. Additionally, administrators should allocate budgets to improve buildings and audiovisual equipment, and relevant organizations should establish policies to promote learning on these issues in educational institutions. Essential lessons from this study can provide a starting point for executives and public health personnel worldwide to apply to develop educational strategies for cancer education and cancer prevention and control.

The Trend in Mitigation Strategies of 3-Monochloropropane-1,2-diol and Glycidyl Esters in Edible Vegetable Oils: Today and Tomorrow.

3-Monochloropropane-1,2-diol (3-MCPD) and its esters, which have carcinogenic and genotoxic effects, are contaminants induced by high-temperature that have been detected in refined oils and fatty foods. 3-MCPD esters, chlorinated propanols, were first identified in 1978 in acid-hydrolysed vegetable proteins used as flavour enhancers in many foods. Glycidyl esters (GE) are contaminants that can occur in edible oils during heat treatment and are formed mainly during the deodorisation phase of refining. The International Agency for Research on Cancer has classified 3-MCPD as a 'potential carcinogen for humans' in group 2B. Glycidol has also been classified as group 2A with mutagenic and carcinogenic properties, i.e. 'probably carcinogenic to humans'. In addition, glycidol has been classified by the International Agency for Research on Cancer (IARC) as a 'possible human carcinogen' (group 2A). Toxicological studies have shown that these genotoxic and carcinogenic contaminants induced by heat treatment are released in the gastrointestinal tract and cause the formation of tumours. In this review the mechanisms of formation, toxicological effects of 3-MCPD and GE on human health, and methods of their detection are shown. The latest strategies to mitigate and prevent 3-MCPD and GE formation during crude oil production, refining and beyond are also discussed.

Seasonal Variation of (Benzo[a]Pyrene) in Ambient Air of Urban to Peri-urban Areas of Panvel Municipal Corporation, Raigad with Reference to Particulate Matter

Polyaromatic Hydrocarbons (PAHs) in the environment have been linked to severe health effects. This study aims to assess the atmospheric pollutant and analyze the variation in PAHs, focussed on benzo[a]pyrene [B(a)P]. Among all PAHs, B(a)P is regarded as a marker for human carcinogenicity. This study reflects the B(a)P concentration and its correlation with the particulate matter (PM10 and PM2.5) in rural, peri-urban, and urban areas of Panvel Municipal Corporation, Maharashtra, India. Samples were collected during the pre & post-monsoon season for two consecutive years (Yr. 2020 and Yr. 2021). B(a)P level was determined using high-performance liquid chromatography coupled with a diode array detector. It was observed that PM2.5 and PM10 show a strong positive correlation (r=0.8-0.9) with B(a)P. It is observed that B(a)P concentrations were high in pre-monsoon w.r.t. post-monsoon, and this concentration increased spatially as we moved from rural to urban areas. Pre-monsoon B(a)P concentration varies somewhat by 5% between rural to urban areas as compared to post-monsoon. High levels of vehicular emissions and industry were associated with the distribution of B(a)P in urban areas, whereas a combination of local emissions and metropolitan area diffusion was responsible for the presence of B(a)P in peri-urban and rural areas. Also, this study captures the variation of B(a)P levels during the period of COVID-19. In future studies, Artificial Intelligence (AI) can augment the determination of PAHs in soil by improving the accuracy and speed of analysis using predictive modeling based on different input parameters to determine outliers in soil PAH data, building sensor networks for real-time monitoring of PAH levels, leverage robotics for automated sample preparations, and rapid testing of samples to identify hotspots.

A single-use electrochemical biosensor system for ultrasensitive detection of Aflatoxin B1 in rice, corn, milk, peanut, chili pepper samples

Aflatoxin B1, a common food contaminant in peanuts and corn and a genotoxic carcinogen in humans poses a significant risk for hepatocellular carcinoma, making its detection crucial; this study aims to develop a label-free electrochemical biosensor using a disposable indium tin oxide polyethylene terephthalate (ITO-PET) electrode modified with 3-Aminopropyltriethoxysilane for detecting Aflatoxin B1 in real food samples. Initially, optimization steps for the proposed biosensor were conducted using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques. Characterization steps such as storage capacity, regeneration, and single frequency impedance (SFI) were completed for the proposed disposable biosensor after the optimization steps. The electrochemical biosensor, based on AFB1, exhibited excellent repeatability and reproducibility. It had a broad dynamic detection range from 0.1 fg/mL to 500 fg/mL, with low limits of detection (LOD) and quantitation (LOQ) at 0.19 fg/mL and 0.65 fg/mL, respectively. Finally, the proposed AFB1-based biosensor system was applied to real food samples (rice, chili pepper, milk, corn, and peanuts) for testing and validation.

Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen

Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and multiple toxic effects have been shown to be associated with As exposure. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic injury. In this study, a Sprague-Dawley (SD) rat model of As-poisoned was established, aiming to explore the molecular mechanism of As-induced immune injury through the combined analysis of proteomics and metabolomics of rats’ spleen. After feeding the rats with As diet (50 mg/kg) for 90 days, the spleen tissue of the rats in the As-poisoned group was damaged, the level of As was significantly higher than that of the control group (P < 0.001), and the level of inflammatory cytokine interleukin-6 (IL-6) was decreased (P < 0.01). Proteomics and metabolomics results showed that a total of 134 differentially expressed proteins (DEPs) (P < 0.05 and fold change > 1.2) and 182 differentially expressed metabolites (DEMs) (VIP >1 and P < 0.05) were identified in the spleens of the As poisoned group compared to the control group (As/Ctrl). The proteomic results highlight the role of hypoxia-inducible factors (HIF), natural killer cell mediated cytotoxicity, and ribosomes. The major pathways of metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism and folate single-carbon pool. The integrated analysis of these two omics suggested that Hmox1, Stat3, arachidonic acid, phosphatidylcholine and leukotriene B4 may play key roles in the mechanism of immune injury to the spleen by As exposure. The results indicate that As exposure can cause spleen damage in rats. Through proteomic and metabolomic analysis, the key proteins and metabolites and their associated mechanisms were obtained, which provided a basis for further understanding of the molecular mechanism of spleen immune damage caused by As exposure.

QM-CSA: A Novel Quantum Mechanics-Based Protocol for Evaluation of the Carcinogen-Scavenging Activity of Polyphenolic Compounds.

In this study, a novel quantum mechanics-based protocol for the evaluation of carcinogen-scavenging activity (QM-CSA) is developed. The QM-CSA protocol represents a universal and quantitative approach to evaluate and compare the activation-free energies for alkylation reactions between individual polyphenolic compounds and chemical carcinogens of the epoxy type at physiological conditions by applying two scales: the absolute scale allowing for the comparison with guanine and the relative scale allowing the comparison with glutathione as a reference compound. The devised quantum mechanical methodology was validated by comparing the activation-free energies calculated with 14 DFT functionals in conjunction with two implicit solvation models (SMD and CPCM) and the experimental activation-free energies for reactions between nine investigated chemical carcinogens and guanine. According to the obtained results, the best agreement with experimental data was achieved by applying DFT functionals M11-L and MN12-L in conjunction with the flexible 6-311++G(d,p) basis set and implicit solvation model SMD, and the obtained uncertainties were proven to be similar to the experimental ones. To demonstrate the applicability of the QM-CSA protocol, functionals M11-L, and MN12-L in conjunction with the SMD implicit solvation model were applied to calculate activation-free energies for the reactions of nine investigated chemical carcinogens of the epoxy type with three catechins, namely EGCG, EGC, and (+)-catechin. The order of CSA in this series of catechins in comparison to guanine and glutathione was determined as (+)-catechin > EGC > EGCG. The obtained results, for the first time, demonstrated the evaluation and comparison of CSA in a series of selected catechins with respect to glutathione and guanine. Moreover, the presented results provide valuable insights into the reaction mechanisms and configurations of the corresponding transition states. The novel QM-CSA protocol is also expected to expand the kinetic data for alkylation reactions between various polyphenolic compounds and chemical carcinogens of the epoxy type, which is currently lacking in the scientific literature.

Determination of Total Aflatoxins in Polished Rice by Liquid Chromatography-Fluorescence Detection with Multifunctional Column Cleanup and Precolumn Derivatization: Single-Laboratory and Inter-Laboratory Validation Studies.

Aflatoxins are toxic metabolites produced by Aspergillus spp. Because aflatoxins are potent carcinogens in humans and animals, many countries have set regulatory limits for aflatoxins in foods to prevent dietary exposure. From a global food safety perspective, in 2023, the Codex Alimentarius Commission established the maximum level (ML) of total aflatoxins in certain cereals and cereal-based products, including polished rice. Therefore, validated analytical methods for aflatoxin detection are necessary. In this study, a high performance liquid chromatography (HPLC)-fluorescence method coupled with multifunctional column clean-up and trifluoroacetic acid derivatization was developed for the determination of aflatoxin levels in polished rice. Our method was validated in a single laboratory study using aflatoxin-spiked materials, followed by an inter-laboratory validation study. Twelve laboratories participated in the inter-laboratory validation study, and five polished rice test samples artificially contaminated with aflatoxins were analyzed. In a single laboratory study, the ranges of mean recoveries of aflatoxin B1, B2, G1, G2, and total aflatoxins were 101%, 100-103%, 93-96%, 95-98%, and 97-99%, respectively. The relative standard deviations for within-day and between-day variations were all ≤ 4.4%. In the inter-laboratory validation study, the relative standard deviations for repeatability and reproducibility were from 0.7 to 2.7% and 3.3 to 8.9% for all analytes, respectively. In response to the Codex ML and method performance criteria for aflatoxins in polished rice, an analytical method based on HPLC-fluorescence detection was developed. All method performance parameters estimated from the testing results of the single-laboratory and inter-laboratory validation studies met the criteria required by the Codex. Single- and inter-laboratory studies for the validation of an analytical method for aflatoxin level determination in polished rice were successfully performed. This analytical method will be suitable to determine aflatoxin levels around the Codex ML set for polished rice.

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study

BackgroundChemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S. cohort. MethodsWe used the U.S. Environmental Protection Agency’s Toxics Release Inventory to estimate historical airborne emissions (1987–1995) of 19 known and probable carcinogens for participants enrolled (1995–1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status. ResultsWe observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34–3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92–1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94–1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89–1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01–1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status. ConclusionsAn increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.