Carcinogenic Potential Research Articles

Overview of the pesticide contamination provided by the last Brazilian water quality surveillance information system for human consumption (SISÁGUA 2022) report

The Water Quality Surveillance Information System for Human Consumption (SISÁGUA) is designed to manage the risks of water contamination for human consumption. This short communication focuses on data from the 2022 Report regarding pesticide analysis. The data centers on 27 active pesticide ingredients found in drinking water samples exceeding the maximum residual limits (MRLs) established by Brazilian legislation. Results indicate that 1609 municipalities (60 %) found at least one pesticide in their water. Two hundred ten municipalities detected all 27 pesticides tested, with 11 of these pesticides reported to have some carcinogenic potential. Nearly one and a half million people were exposed to levels above the Brazilian MRL, with the sum of maximum detected residues exceeding 80,000 ppb. Additionally, the report highlights that 53 % of Brazilian municipalities did not submit water monitoring data for human consumption. Thus, improving and expanding the scope of water analysis within the SISÁGUA framework is essential.

Exposure to pesticides in Chile and its relationship with carcinogenic potential: a review

Exposure to pesticides in Chile and its relationship with carcinogenic potential: a review

Adsorption of Polycyclic Aromatic Hydrocarbons from Wastewater Using Iron Oxide Nanomaterials Recovered from Acid Mine Water: A Review

Polycyclic aromatic hydrocarbons (PAHs) are a group of organic pollutants known for their persistence and potential carcinogenicity. Effective removal techniques are required since their presence in wastewater poses serious threats to human health and the environment. In this review study, iron oxide nanomaterials (IONs), a by-product of mining operations, recovered from acid mine water are used to investigate the adsorption of PAHs from wastewater. The mechanisms of PAH adsorption onto IONs are investigated, with a focus on the effects of concentration, temperature, and pH on adsorption efficiency. The better performance, affordability, and reusable nature of IONs are demonstrated by comparative studies with alternative adsorbents such as activated carbon. Economic and environmental ramifications highlight the benefits of employing recovered materials, while case studies and real-world applications show how effective IONs are in removing PAHs in the real world. This review concludes by discussing potential future developments in synthesis processes, areas for more research, and emerging trends in nanomaterial-based adsorption. This research intends to contribute to the development of more effective and sustainable wastewater treatment technologies by offering a thorough assessment of the present and future potential of employing IONs for PAH removal from wastewater.

Malignant Transformation of Abdominal Wall Endometriosis: A Case Report

Background: The carcinogenic potential of parietal endometriosis is poorly understood, making it difficult to diagnose and uncertain how to treat it. The prognosis for this complication of an abdominal scar is rather poor. In the literature, the survival rate only reaches 57% with a short follow-up of 20 months. The most common histological form is clear cell carcinoma, followed by endometrioid carcinoma. Radical surgery is the main treatment. Good operating technique with appropriate care during cesarean sections can prevent this complication of endometriosis. The starting point is usually a caesarean section scar. We report the case of a 44-year-old woman with a history of caesarean section who presented with recurrent parietal endometriosis, which transformed into clear cell adenocarcinoma.

A magnetic carboxyl-functionalized covalent organic framework for the efficient enrichment of foodborne heterocyclic aromatic amines prior to UPLC-MS analysis

Foodborne heterocyclic aromatic amines (HAAs) are potent mutagens and carcinogens, posing significant health risks. Existing enrichment methods for HAAs need better adsorption selectivity and capacity for daily exposure assessment. This study hypothesized that introducing carboxylic groups into magnetic covalent organic frameworks (m-COFs) would improve HAAs adsorption by providing additional binding sites. Hence, we prepared a novel magnetic adsorbent, termed as Fe3O4@DOPA-TpPa-(COOH)2 capable of enhancing the HAAs detection through magnetic solid-phase extraction (MSPE) coupled with UPLC-MS. This sorbent demonstrated a large specific surface area (130.7 m2/g), high magnetic responsivity (21.05 emu/g), and robust stability, with an adsorption capacity (Qm[cal]: 81.82 mg/g) driven by electrostatic, LP − π/C-H − π interactions, and hydrogen bonding. Optimal MSPE conditions provided sensitive detection with a broad linear range (5–500 ng/mL), low limits of detection (0.01–7.01 ng/g), and excellent repeatability. Application to Cantonese mooncake samples showed satisfactory recoveries (62.12%–126.86%). This method offers a more accurate tool for detecting HAAs.

Source apportionment of particle-bound polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs (OPAHs), and their associated long-term health risks in a major European city

Many studies have drawn attention to the associations of oxygenated polycyclic aromatic hydrocarbons (OPAHs) with harmful health effects, advocating for their systematic monitoring alongside simple PAHs to better understand the aerosol carcinogenic potential in urban areas. To address this need, this study conducted an extensive PM2.5 sampling campaign in Athens, Greece, at the Thissio Supersite of the National Observatory of Athens, from December 2018 to July 2021, aiming to characterize the levels and variability of polycyclic aromatic compounds (PACs), perform source apportionment, and assess health risk. Cumulative OPAH concentrations (Σ-OPAHs) were in the same range as Σ-PAHs (annual average 4.2 and 5.6 ng m−3, respectively). They exhibited a common seasonal profile with enhanced levels during the heating seasons, primarily attributed to residential wood burning (RWB). The episodic impact of biomass burning was also observed during a peri-urban wildfire event in May 2021, when PAH and OPAH concentrations increased by a factor of three compared to the monthly average. The study period also included the winter 2020–2021 COVID-19 lockdown, during which PAH and OPAH levels decreased by >50 % compared to past winters. Positive matrix factorization (PMF) source apportionment, based on a carbonaceous aerosol speciation dataset, identified PAC sources related to RWB, local traffic (gasoline vehicles) and urban traffic (including diesel emissions), as well as an impact of regional organic aerosol. Despite its seasonal character, RWB accounted for nearly half of Σ-PAH and over two-thirds of Σ-OPAH concentrations. Using the estimated source profiles and contributions, the source-specific carcinogenic potency of the studied PACs was calculated, revealing that almost 50 % was related to RWB. These findings underscore the urgent need to regulate domestic biomass burning at a European level, which can provide concrete benefits for improving urban air quality, towards the new stricter EU standards, and reducing long-term health effects.

Novel method for monitoring of carcinogenic impurity of N-nitrosamine in nizatidine pharmaceutical products using ultra high-pressure liquid chromatography triple quadrupole mass spectrometry.

Nitrosamine compounds pose a significant concern as potential carcinogens, prompting heightened scrutiny from regulatory bodies, particularly regarding their presence in pharmaceuticals. The detection of unacceptable levels of N-nitrosodiethylamine (NDMA) in ranitidine has led to widespread recalls, driving interest in alternative medications such as nizatidine, which shares a similar pharmacological class and is used to treat various gastrointestinal conditions. Despite fewer reports on NDMA levels in nizatidine, its structural similarity to ranitidine, characterized by a tertiary amine, underscores the potential for NDMA formation. Addressing the analytical challenges associated with nitrosamine detection, this study focuses on developing and validating an ultra-high pressure liquid chromatography triple quadrupole mass spectrometry (UHPLC-MS/MS) method for quantifying NDMA in both nizatidine active pharmaceutical ingredients and tablet formulations. Method validation adheres to International Council for Harmonisation recommendations, with a demonstrated linear range of 0.25-100 ng/mL for NDMA, exhibiting excellent linearity (regression coefficient >0.999) and efficient recovery rates ranging from 95.98% to 109.57%. The method shows high sensitivity, with limits of detection and quantification of 0.25 and 0.5ng/mL, respectively. The developed UHPLC-MS/MS method offers a simple, precise, accurate, and selective approach for monitoring NDMA levels in nizatidine formulations available in Australia, promising enhanced sensitivity and specificity with limits of quantification in the ppb and sub-ppb ranges.

A biosensor integrating the electrochemical and fluorescence strategies for detection of aflatoxin B1 based on a dual-functionalized platform

BackgroundAflatoxin B1 (AFB1), is a potent hepatic carcinogen which causes cancer by inducing DNA changes in the liver cells. Variety of methods have been developed for detection of AFB1 which are based on single mode detection strategy. Fabrication of novel platform which are compatible for multimodal detection of AFB1 provide robust performance for reliable detection of AFB1. In this study, we aimed to develop a robust biosensing platform that combines electrochemical and fluorescence techniques for the sensitive and specific detection of Aflatoxin B1. ResultsThe sensing platform includes the magnetic core-shell Fe3O4@AuNPs and zeolitic imidazolate framework-8 (ZIF-8). In electrochemical mode, the applied voltametric approach was used through functionalization of glassy carbon electrode and exhibited a linear range between 0.5 and 10000 pg mL−1 with LOD of 0.32 pg mL−1. Fluorescence analysis was based on the FRET on/off status of FAM-functionalized aptamer deposited on the same platform. The FAM emission recovered by the addition of AFB1 concentration in the range of 6–60 fg mL−1 with the LOD of 0.20 fg mL−1. The real sample analysis demonstrated satisfactory relative recoveries in the range of 92.81–105.32 % and 91.66–106.66 % using the electrochemical and fluorescence methods, respectively, and its reliability was confirmed by the HPLC technique. SignificanceThe experimental results affirm that the proposed aptasensor serves as a sensitive, efficient, and precise platform for monitoring AFB1 in both electrochemical and fluorescence detection approaches. Proposed strategy showed efficient selectivity among different analytes and was reproducible. Furthermore, the applicability of biosensor was confirmed in food and biological samples.

Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review.

As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.

Toxicological Assessment of Azo Dye Brown HT In Vivo

Background: Azo dyes, widely used in food, pharmaceuticals, textiles, and cosmetics, raise significant safety concerns due to their potential toxicological effects. Specifically, the biotransformation of azo dyes into aromatic amines, which may have carcinogenic potential, necessitates an investigation into their impact on health, especially for vulnerable populations like children. Methods: This study assessed the effects of Brown HT (E155) azo dye on juvenile rats. Male Long-Evans rats were divided into control and treatment groups, receiving varying doses of Brown HT over six weeks. Parameters measured included body weight, hematological and biochemical indices, and histopathological changes in liver and kidney tissues. Results: The results indicated a significant dose-dependent effect of Brown HT on body weight, blood parameters, and organ function. The high-dose group exhibited significant weight reduction, elevated liver enzymes, and abnormal lipid profiles. Histopathological examination revealed severe liver damage and renal impairment in high-dose groups, indicating potential long-term health risks associated with azo dye consumption. Conclusion: Brown HT azo dye demonstrates dose-dependent toxicity in juvenile rats, impacting physiological, biochemical, and histopathological parameters. These findings underscore the need for regulatory scrutiny regarding azo dye usage in food products, particularly for children, to mitigate associated health risks and promote safer food practices.

Is Cadmium Genotoxicity Due to the Induction of Redox Stress and Inflammation? A Systematic Review.

The transition metal cadmium (Cd) is toxic to humans and can induce cellular redox stress and inflammation. Cd is a recognized carcinogen, but the molecular mechanisms associated with its genotoxicity and carcinogenicity are not defined. Therefore, a systematic review was undertaken to examine the scientific literature that has covered the molecular mechanism of Cd genotoxicity and its relationship to cellular redox stress and inflammation. An electronic database search of PubMed, Scopus, and the Web of Science Core Collection was conducted to retrieve the studies that had investigated if Cd genotoxicity was directly linked to the induction of redox stress and inflammation. Studies included exposure to Cd via in vitro and in vivo routes of administration. Of 214 publications retrieved, 10 met the inclusion criteria for this review. Preclinical studies indicate that Cd exposure causes the induction of reactive oxygen species (ROS) and, via concomitant activity of the transcription factor NF-κβ, induces the production of pro-inflammatory cytokines and a cytokine profile consistent with the induction of an allergic response. There is limited information regarding the impact of Cd on cellular signal transduction pathways, and the relationship of this to genotoxicity is still inconclusive. Nevertheless, pre-incubation with the antioxidants, N-acetylcysteine or sulforaphane, or the necroptosis inhibitor, necrostatin-1, reduces Cd toxicity; indicative that these agents may be a beneficial treatment adjunct in cases of Cd poisoning. Collectively, this review highlights that Cd-induced toxicity and associated tissue pathology, and ultimately the carcinogenic potential of Cd, may be driven by redox stress and inflammatory mechanisms.

Sulfuric acid-induced skin neoplasms in immunocompetent mice.

This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 μm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki-67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure.

Improving the Assessment of Risk Factors Relevant to Potential Carcinogenicity of Gene Therapies: A Consensus Article.

Regulators and industry are actively seeking improvements and alternatives to current models and approaches to evaluate potential carcinogenicity of gene therapies (GTs). A meeting of invited experts was organized by NC3Rs/UKEMS (London, March 2023) to discuss this topic. This article describes the consensus reached among delegates on the definition of vector genotoxicity, sources of uncertainty, suitable toxicological endpoints for genotoxic assessment of GTs, and future research needs. The collected recommendations should inform the further development of regulatory guidelines for the nonclinical toxicological assessment of GT products.

Overrepresentation of New Workers in Jobs with Multiple Carcinogen Exposures in Canada.

Background. In Canada, understanding the demographic and job-related factors influencing the prevalence of new workers and their exposure to potential carcinogens is crucial for improving workplace safety and guiding policy interventions. Methods. Logistic regression was performed on the 2017 Labour Force Survey (LFS), to estimate the likelihood of being a new worker based on age, industry, occupation, season, and immigration status. Participants were categorized by sector and occupation using the North American Industry Classification System (NAICS) 2017 Version 1.0 and National Occupational Classification (NOC) system 2016 Version 1.0. Finally, an exposures-per-worker metric was used to highlight the hazardous exposures new workers encounter in their jobs and industries. Results. Individuals younger than 25 years had 3.24 times the odds of being new workers compared to those in the 25-39 age group (adjusted odds ratios (OR) = 3.24, 95% confidence interval (95% CI) = 3.18, 3.31). Recent immigrants (less than 10 years in the country) were more likely to be new workers than those with Canadian citizenship (OR 1.36, 95% CI: 1.32, 1.41). The total workforce exposures-per-worker metric using CAREX Canada data was 0.56. By occupation, new workers were the most overrepresented in jobs in natural resources and agriculture (20.5% new workers), where they also experienced a high exposures-per-worker metric (1.57). Conclusions. Younger workers (under 25 years) and recent immigrants who had arrived 10 or fewer years prior were more likely to be new workers, and were overrepresented in jobs with more frequent hazardous exposures (Construction, Agriculture, and Trades).

Gut microbiota carcinogen metabolism causes distal tissue tumours

Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.

Impact of processed and ultra-processed foods on colorectal cancer risk: Mechanisms, dietary factors, and protective compound

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide, linked to behavioral factors such as a sedentary lifestyle and smoking, environmental factors like pollution, and nutritional factors including a diet rich in red and processed meats. Some foods are associated with potential carcinogenicity, while others act as protective factors. This review aims to report the contribution of processed and ultra-processed foods to the etiopathogenesis of CRC and explore the role of protective diets. The article is an integrative review conducted in PubMed and VHL databases using the descriptors “colorectal cancer” and “processed foods.” Studies published in the last five years addressing the relationship between these foods and CRC development were included. Potentially carcinogenic substances in processed foods, such as heterocyclic amines, nitrosamines, heme iron, industrial fatty acids, aromatic hydrocarbons, sialic acid sugar, and additives like titanium dioxide, were associated with colon and rectal neoplasms. Additional associations were found with the human microbiome, packaging materials, and food preparation methods. Conversely, several food components can protect against CRC. The consumption of processed and ultra-processed foods can significantly increase CRC risk through mechanisms like inflammation, oxidative stress, gene expression changes, and genetic material damage. The intestinal flora profile may be protective against CRC but is altered when processed and ultra-processed foods are included in the diet. Fiber, phytochemicals, and spices present in plant foods are consistently reported to have anticarcinogenic effects.

The Relationship Between Metal Exposure and HPV Infection: Evidence from Explainable Machine Learning Methods.

HPV is a ubiquitous pathogen implicated in cervical and other cancers. Although vaccines are available, they do not encompass all subtypes. Meanwhile, metal exposure may elevate the risk of HPV infection and amplify its carcinogenic potential, but studies to further elucidate this relationship are insufficient.This study entailed a cross-sectional analysis utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. The study sample comprised 2765 women. Multivariate logistic regression was employed to examine the association between single metal exposure and HPV infection, weighted quantile sum (WQS) regression was utilized for assessing the mixed metal exposure effect, and the XGBoost + SHapley Additive exPlanations (SHAP) to evaluate the contribution of metal exposure in HPV infection.Multivariate logistic regression analysis indicated that elevated Co concentration was inversely associated with HPV infection (OR 0.891; 95% CI 0.814-0.975), while elevated Pb concentration correlated with an increased HPV infection (OR 1.176; 95% CI 1.074-1.287). Regression analysis of the WQS for mixed metal exposure suggested that the WQS index was potentially linked to an increased likelihood of HPV infection in the positive direction (OR 1.249; 95% CI 1.052-1.482), with no significant association observed in the negative direction (OR 0.852; 95% CI 0.713-1.017). SHAP analysis prioritized the importance of characteristics: number of sexual partners, marital status, poverty-to-income ratio (PIR), Co, Pb, and alcohol consumption.Exposure to Pb was associated with an increase in the incidence of HPV infection, whereas Co exposure demonstrated an inverse relationship. The composite exposure to multiple metals showed a positive association with the prevalence of HPV infection. These findings indicate that exposure to metals could potentially escalate the prevalence of HPV infection.

A Kinetic Model for Assessing Potential Nitrosamine Carcinogenicity.

Understanding the potential carcinogenic potency of nitrosamines is necessary to setting acceptable intake limits. Nitrosamines and the components that can form them are commonly present in food, water, cosmetics, and tobacco. The recent observation of nitrosamines in pharmaceuticals highlighted the need for effective methods to determine acceptable intake limits. Herein, we describe two computational models that utilize properties based upon quantum mechanical calculations in conjunction with mechanistic insights and established data to determine the carcinogenic potency of a variety of common nitrosamines. These models can be applied to experimentally untested nitrosamines to aid in the establishment of acceptable intake limits.

In Silico Toxicological Analysis of Active Compounds Present in Selected Pesticides Sold in South-West Nigeria

Introduction: The study investigated the molecular effects of human exposure to commonly used pesticides in Nigeria. Methods: Utilizing computational methods like clustering analysis, toxicokinetic predictions, molecular docking, and molecular dynamic (MD) simulation, various health impacts were identified. Results and Discussion: The results revealed significant gastrointestinal absorption, P-glycoprotein bypass, blood-brain barrier penetration, and cytochrome P450 inhibition for certain pesticide agents. Notably, oxathiapiprolin showed hepatotoxicity, propanil exhibited drug-induced liver injury (DILI), and 2,4-dichloro-phenoxyacetic acid demonstrated carcinogenicity. Respiratory toxicity was predicted for most pesticides, except propanil and N-(2,6-diethylphenyl) acetamide. Molecular targets were identified, such as bifenthrin targeting programmed cell death 1 ligand 1 and Atrazine targeting potassium voltage-gated channel subfamily H member 3. Binding affinities were computed, with oxathiapiprolin showing -6.526 kcal/mol with short transient receptor potential channel 7. Molecular dynamic simulations indicated significant binding energy changes over time. Atrazine's binding with potassium voltage-gated channel subfamily H member 3 exhibited a total binding energy ΔGbind of -39.410 kcal/mol and -49.135 kcal/mol at 0 ns and 100 ns, respectively. Oxathiapiprolin's binding with short transient receptor potential channel 7 showed ΔGbind of -53.481 kcal/mol and -44.122 kcal/mol at 0 ns and 100 ns. Conclusion: This study suggests potential hepatotoxicity and carcinogenicity of certain pesticides, emphasizing the need for environmental monitoring and stringent regulations to safeguard public health.

An insight into carcinogenic activity and molecular mechanisms of Bis(2-ethylhexyl) phthalate.

Di(ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant to which humans are exposed via multiple routes. Human health risk assessments for this substance have recently been updated, focusing on reproductive toxicity, including DEHP, in the list of chemicals classified as carcinogenic, mutagenic, or toxic to reproduction (CMR). Moreover, DEHP has also been defined as probably and possibly carcinogenic to humans based on its carcinogenicity in rodents. However, the mechanism of action of DEHP and its relevance in humans remain unclear. Rodent data suggests that DEHP induces cancer through non-genotoxic mechanisms related to multiple molecular signals, including PPARα activation, perturbation of fatty acid metabolism, induction of cell proliferation, decreased apoptosis, production of reactive oxygen species, and oxidative stress. According to the DEHP toxicological dataset, several in vitro cell transformation assays have been performed using different protocols and cellular models to produce different results. This study aimed to evaluate the carcinogenic potential of DEHP by using the A31-1-1 BALB/c-3T3 cell line in a standard cell transformation assay. Additionally, transcriptomic analysis was performed to explore the molecular responses and identify the affected toxicological pathways. Although DEHP treatment did not induce transformation in BALB/c-3T3 cells, the transcriptomic results revealed significant modulation of several pathways associated with DEHP metabolism, tissue-specific functions related to systemic metabolism, and basal cellular signaling with pleiotropic outcomes. Among these signaling pathways, modulation of cell-regulating signaling pathways, such as Notch, Wnt, and TGF-β, can be highlighted. More specific modulation of such genes and pathways with double functions in metabolism and neurophysiology underlies the well-known crosstalk that may be crucial for the mechanism of action of DEHP. Our findings offer evidence to support the notion that these models are effective in minimizing the use of animal testing for toxicity assessment.