Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

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-ß, 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.

Systematic review of mechanistic evidence for TiO2 nanoparticle-induced lung carcinogenicity.

Nano-sized titanium dioxide particles (TiO2 NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO2 NPs in the lung are still unclear despite the vast number of in vitro and in vivo studies investigating TiO2 NPs. Here, we systematically reviewed the existing in vitro and in vivo mechanistic evidence of TiO2 NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens. A total of 346 studies qualified for the quality and reliability assessment, of which 206 were considered good quality. Using a weight-of-evidence approach, these studies provided mainly moderate to high confidence for the biological endpoints regarding genotoxicity, oxidative stress and chronic inflammation. A limited number of studies investigated other endpoints important to carcinogenesis, relating to proliferation and transformation, epigenetic alterations and receptor-mediated effects. In summary, TiO2 NPs might possess the ability to induce chronic inflammation and oxidative stress, but it was challenging to compare the findings in the studies due to the wide variety of TiO2 NPs differing in their physicochemical characteristics, formulation, exposure scenarios/test systems, and experimental protocols. Given the limited number of high-quality and high-reliability studies identified within this review, there is a lack of good enough mechanistic evidence for TiO2 NP lung carcinogenicity. Future toxicology/carcinogenicity research must consider including positive controls, endotoxin testing (where necessary), statistical power analysis, and relevant biological endpoints, to improve the study quality and provide reliable data for evaluating TiO2 NP-induced lung carcinogenicity.

Metabolic Carcinogenesis.

Several types of environmental, chemical and metabolic carcinogens exist both exogenously and endogenously. Humans are daily exposed to aforementioned carcinogens through various sources such as through water, air and food or through metabolic and inflammatory products. This chapter will summarize the links between exogenous and endogenous carcinogen exposure and their metabolism with the cancer pathogenesis and associated risks. This chapter will also cover the carcinogens acquired through lifestyle factors like tobacco use and occupational exposures to different chemicals like asbestos, arsenic, chloroform, vinyl chloride, etc. Moreover, environmental carcinogens such as radiation, sunlight, diet, smoke, etc. will also be discussed in this chapter. Furthermore, there are certain carcinogens that require bio-activation and various human enzymes that play a vital role in the metabolic carcinogenesis will also be recapitulated. Necessary preventive measures against carcinogenic exposure from the exogenous environment are significant to be taken into account to reduce the risks associated with the carcinogens.

In silico attempt to reveal the link between cancer development and combined exposure to the maize herbicides: Glyphosate, nicosulfuron, S-metolachlor and terbuthylazine.

Pesticides are crucial for crop protection and have seen a 50 % increase in use in the last decade. Besides preventing significant crop losses their use has raised health concerns due to consumer exposure through residues in food and water. The toxicity data from individual components is often used to assess overall mixture toxicity, but uncertainty persists in understanding the behaviors of individual chemicals within these mixtures. Assessing the risk of pesticide mixture exposure remains challenging, potentially leading to overestimation or underestimation of toxicity. This study aims to establish a possible link between exposure to a herbicide mixture and genotoxic effects, focusing on cancer development. Our analysis was focused on four herbicides glyphosate, nicosulfuron, S-metolachlor and terbuthylazine. To determine the link between genes associated with cancer development due to exposure to herbicide mixture, a CTD database tools were used. Through the ToppFun tool molecular function and biological process associated with genes common to the disease of interest and selected herbicides were evaluated. And finally, GeneMANIA was used in order to analyze the function and interaction between common genes of herbicide mixture. Among the 7 common genes for herbicide mixture and cancer development coexpression characteristics were dominant at 65.41 %, 22.14 % of annotated genes shared the same pathway and 7.88 % showed co-localization. Among six target genes involved in genetic disease development co-expression was dominant at 87.34 %, colocalization at 8.03 % and shared protein domains at 4.52 %. Comprehensive molecular analyses, encompassing genomics, proteomics, and pathway analysis, are essential to unravel the specific mechanisms involved in the context of the studied mixture and its potential carcinogenic effects.

The burden of lung cancer and mortality attributable to occupational risk factors between 1990 and 2019 in Brazil and federative units.

OBJECTIVE: The aim of this study was to analyse the attributable risk of mortality and DALYs (Disability Adjusted Life Years) due to occupational carcinogens for lung cancer between 1990 and 2019 in Brazil and federation units, as well as its relationship with the Socio-demographic Index (SDI). STUDY DESIGN: Epidemiological study. METHODS: This is an epidemiological study that used GBD 2019 (Global Burden of Disease Study) estimates of lung cancer mortality rates and DALYs attributable to occupational carcinogens. The relationship between these rates and SDI was assessed using panel data analysis. RESULTS: In Brazil, occupational exposure to asbestos, silica and diesel vapours accounted for more than 85.00% of lung cancer deaths and DALYs attributable to occupational carcinogens in both sexes between 1990 and 2019. An increase in both rates was observed in women for almost all the occupational carcinogens assessed, especially in the North and Northeast regions of the country, with diesel vapours standing out the most. CONCLUSIONS: The present study highlighted the urge to characterise exposure to occupational risks for lung cancer, especially for the female population in the North and Northeast regions of Brazil.

Occupational exposure to welding fume in Australia: An online survey.

OBJECTIVE: This survey aimed to investigate exposure to welding fume in Australian workplaces and the use of protective and control measures among workers. METHODS: Data were collected via a cross-sectional online survey of workers and employers involved in welding in Australia. Survey questions focused on the determinants of exposure to welding fume, welding experience and qualifications, and use of control measures. RESULTS: There were 634 respondents to the survey across Australia of whom 577 (91%) were assessed as being exposed to welding fume, most at high levels. Welders undertook a wide range of types of welding, and higher-risk welding such as in confined and restricted spaces was common. Most workplaces did not have any form of mechanical ventilation, and use of air-supplied respiratory protection was poor even when ventilation was not used. CONCLUSION: Welders in Australia are exposed to several carcinogens, particularly welding fume, hexavalent chromium (CrVI) and nickel, and the use of control measures is sub-optimal. IMPLICATIONS FOR PUBLIC HEALTH: Higher-order controls are the best way to reduce exposure to carcinogens in the workplace. The lack of use of these controls by Australian welders is concerning and needs to be a focus of attention by regulators and companies.

Benchmarking a universal smoking machine adaptor for tobacco product testing.

SIGNIFICANCE: Characterisation of tobacco product emissions is an important step in assessing their impact on public health. Accurate and repeatable emissions data require that a leak-tight seal be made between the smoking or vaping machine and the mouth-end of the tobacco product being tested. This requirement is challenging because of the variety of tobacco product mouth-end geometries being puffed on by consumers today. We developed and tested a prototype universal smoking machine adaptor (USMA) that interfaces with existing machines and reliably seals with a variety of tobacco product masses and geometries. METHODS: Emissions were machine-generated using the USMA and other available adaptors for a variety of electronic cigarettes (n=7 brands), cigars (n=4), cigarillos (n=2), a heated tobacco product, and a reference cigarette (1R6F), and mainstream total particulate matter (TPM) and nicotine were quantified. Data variability (precision, n≥10 replicates/brand) for all products and error (accuracy) from certified values (1R6F) were compared across adaptors. RESULTS: TPM and nicotine emissions generated using the USMA were accurate, precise and agreed with certified values for the 1R6F reference cigarette. Replicate data indicate that USMA repeatability across all tobacco products tested generally meets or exceeds that from the comparison adaptors and extant data. CONCLUSION: The USMA seals well with a variety of combustible tobacco products, e-cigarettes with differing geometries and plastic-tipped cigarillos. Variability for all measures was similar or smaller for the USMA compared with other adaptors.

Hazard identification of endocrine-disrupting carcinogens (EDCs) in relation to cancers in humans.

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.

The need for research targeting the link between occupational carcinogens and hepatopancreatobiliary cancers in Africa: A systematic review.

INTRODUCTION: Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the association of certain occupational carcinogens in cancer is well established globally, their potential role in HPB cancers remains understudied, especially in an African context. AIM: This systematic review delves into the association between occupational carcinogens and HPB cancer in Africa. It examines the current state of research on occupational carcinogens and HPB cancers in Africa, identifying key challenges and knowledge gaps. METHODS: This systematic review examined publications (published between 01 January 2012 and 31 May 2023) that highlight occupational carcinogens and HBP cancers in Africa. The search was conducted on electronic databases namely PubMed, Web of Science, and Africa Wide Information. RESULT: Due to the lack of information on the association between occupational carcinogens and HPB cancers in Africa, as a result of the paucity of published studies, only four articles were included in this study. Hepatocellular carcinoma (HCC) was the predominant cancer associated with the occupational carcinogen, aflatoxin. Agricultural workers, especially those involved in the production and processing of maize and peanuts, appear to be the most exposed to aflatoxin. CONCLUSION: Despite the sample size limitations due to the paucity of research studies on occupational carcinogens and HPB cancers in Africa, this study provides a reasonable tool for subsequent epidemiological studies. There is a need for more research on the association of occupational carcinogens and HPB cancers in Africa, especially with the growing industrialization.

Understanding the heterocyclic aromatic amines: An overview and recent findings.

Heterocyclic aromatic amines (HAAs) constitute a group of highly toxic organic compounds strongly associated with the onset of various types of cancer. This paper aims to serve as a valuable resource for food scientists working towards a better understanding of these compounds including formation, minimizing strategies, analysis, and toxicity as well as addressing existing gaps in the literature. Despite extensive research conducted on these compounds since their discovery, several aspects remain inadequately understood, necessitating further investigation. These include their formation pathways, toxic mechanisms, effective mitigation strategies, and specific health effects on humans. Nonetheless, recent research has yielded promising results, contributing significantly to our understanding of HAAs by proposing new potential formation pathways and innovative strategies for their reduction.

The Known and Unknown: Investigating the Carcinogenic Potential of Plastic Additives.

Microplastics are routinely ingested and inhaled by humans and other organisms. Despite the frequency of plastic exposure, little is known about its health consequences. Of particular concern are plastic additives─chemical compounds that are intentionally or unintentionally added to plastics to improve functionality or as residual components of plastic production. Additives are often loosely bound to the plastic polymer and may be released during plastic exposures. To better understand the health effects of plastic additives, we performed a comprehensive literature search to compile a list of 2,712 known plastic additives. Then, we performed an integrated toxicogenomic analysis of these additives, utilizing cancer classifications and carcinogenic expression pathways as a primary focus. Screening these substances across two chemical databases revealed two key observations: (1) over 150 plastic additives have known carcinogenicity and (2) the majority (∼90%) of plastic additives lack data on carcinogenic end points. Analyses of additive usage patterns pinpointed specific polymers, functions, and products in which carcinogenic additives reside. Based on published chemical-gene interactions, both carcinogenic additives and additives with unknown carcinogenicity impacted similar biological pathways. The predominant pathways involved DNA damage, apoptosis, the immune response, viral diseases, and cancer. This study underscores the urgent need for a systematic and comprehensive carcinogenicity assessment of plastic additives and regulatory responses to mitigate the potential health risks of plastic exposure.

High throughput and sensitive quantitation of tobacco-specific alkaloids and nitrosamines in wastewater.

Tobacco-specific alkaloids and nitrosamines are important biomarkers for the estimation of tobacco use and human exposure to tobacco-specific nitrosamines that can be monitored by wastewater analysis. Thus far their analysis has used solid phase extraction, which is costly and time-consuming. In this study, we developed a direct injection liquid chromatography-tandem mass spectrometry method for the quantification of two tobacco-specific alkaloids and five nitrosamines in wastewater. The method achieved excellent linearity (R2 > 0.99) for all analytes, with calibration ranging from 0.10 to 800 ng/L. Method limits of detection and quantification were 0.17 ng/L (N-nitrosonornicotine, NNN) and 1.0 ng/L (N-nitrosoanatabine (NAT) and NNN), with acceptable accuracy (100 % ± 20 %) and precision (± 15 %). Analyte loss during filtration was < 15 %, and the relative matrix effect was < 10 %. The method was applied to 43 pooled wastewater samples collected from three wastewater treatment plants in Australia between 2017 and 2021. Anabasine and anatabine were detected in all samples at concentrations of 5.0 - 33 ng/L and 12 - 41 ng/L, respectively. Three of the five tobacco-specific nitrosamines (NAT, NNN, and (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL)) were detected, in < 50 % of the wastewater samples, with concentrations nearly ten times lower than the tobacco alkaloids (< 1.0 - 6.2 ng/L). In-sewer stability of the nitrosamines was also assessed in this study, with four (NAT, NNAL, NNN, and N-nitrosoanabasine (NAB)) being stable (i.e. < 20 % transformation over 12 h in both control reactor (CR) and rising main reactor (RM) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) being moderately stable (< 40 % loss over 12 h in RM). This direct injection method provides a high-throughput approach in simultaneous investigation of tobacco use and assessment of public exposure to tobacco-specific nitrosamines.

Airborne and surface contamination after rotational intraperitoneal pressurized aerosol chemotherapy using cisplatin.

OBJECTIVE: We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. METHODS: We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum. RESULTS: Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves. CONCLUSION: During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.

Structural and mechanistic insights into the transport of aristolochic acids and their active metabolites by human serum albumin.

Aristolochic acids I and II (AA-I/II) are carcinogenic principles of Aristolochia plants, which have been employed in traditional medicinal practices and discovered as food contaminants. While the deleterious effects of AAs are broadly acknowledged, there is a dearth of information to define the mechanisms underlying their carcinogenicity. Following bioactivation in the liver, N-hydroxyaristolactam and N-sulfonyloxyaristolactam metabolites are transported via circulation and elicit carcinogenic effects by reacting with cellular DNA. In this study, we apply DNA adduct analysis, X-ray crystallography, isothermal titration calorimetry, and fluorescence quenching to investigate the role of human serum albumin (HSA) in modulating AA carcinogenicity. We find that HSA extends the half-life and reactivity of N-sulfonyloxyaristolactam-I with DNA, thereby protecting activated AAs from heterolysis. Applying novel pooled plasma HSA crystallization methods, we report high-resolution structures of myristic acid-enriched HSA (HSAMYR) and its AA complexes (HSAMYR/AA-I and HSAMYR/AA-II) at 1.9 Å resolution. While AA-I is located within HSA subdomain IB, AA-II occupies subdomains IIA and IB. ITC binding profiles reveal two distinct AA sites in both complexes with association constants of 1.5 and 0.5 · 106 M-1 for HSA/AA-I versus 8.4 and 9.0 · 105 M-1 for HSA/AA-II. Fluorescence quenching of the HSA Trp214 suggests variable impacts of fatty acids on ligand binding affinities. Collectively, our structural and thermodynamic characterizations yield significant insights into AA binding, transport, toxicity, and potential allostery, critical determinants for elucidating the mechanistic roles of HSA in modulating AA carcinogenicity.

A sustainable, eco-friendly Tb/Eu-modified HOFs for ultrasensitive detection and efficient adsorption of carcinogens in complex water environments.

Developing a multifunctional material that can detect and remove carcinogens in water environments, simultaneously monitor their toxic metabolites in living organisms is significant for environmental remediation and human health. However, most research only focused on detection or adsorption carcinogens due to the difficulty of integrating multiple functions into one material, let alone monitoring their toxic metabolites. Here, a multifunctional Tb/Eu@TATB-HOF (1) is first developed to monitor two carcinogens, malachite green (MG) and its metabolites leucomalachite green (LMG), and simultaneously remove MG from the contaminated water. 1, as the dual-emission fluorescence sensor, can achieve ultrasensitive and highly visualized sensing for MG and LMG with different response modes. Even in actual samples, 1 still exhibits satisfactory sensing performances. As the adsorbent, 1 displays good recyclability and high adsorption capacity for MG. The sensing and adsorption mechanisms are explored through experiments and theoretical calculations. This work not only provides a novel insight for environmental remediation and human health through detection and removal of carcinogens, simultaneously monitoring their toxic metabolites, but first reveals the enormous potential of HOFs as multifunctional materials simultaneously for fluorescence sensing and adsorption.

Pink and Orange Tattoo Pigments: Two Occurrences of Squamous Cell Neoplasms.

This case report covers the case of a 56-year-old woman with two separate occurrences of squamous cell neoplasms, one arising in pink tattoo pigment and another arising in orange tattoo pigment. A review of the literature was conducted to evaluate the prevalence of malignancy occurring in tattoos. This is rare and there are a limited number of case reports and no large studies done on this condition. Most malignancies in tattoos occur in red, black, or blue tattoo inks and no cases have been reported thus far of malignancy in pink or orange tattoo pigments. Due to the limited number of cases, more case studies are needed to determine the prevalence, risk, and epidemiology of malignancy arising within tattoos.

Mouse Models for Head and Neck Squamous Cell Carcinoma.

The prognosis and survival rate of head and neck squamous cell carcinoma (HNSCC) have remained unchanged for years, and the pathogenesis of HNSCC is still not fully understood, necessitating further research. An ideal animal model that accurately replicates the complex microenvironment of HNSCC is urgently needed. Among all the animal models for preclinical cancer research, tumor-bearing mouse models are the best known and widely used due to their high similarity to humans. Currently, mouse models for HNSCC can be broadly categorized into chemical-induced models, genetically engineered mouse models (GEMMs), and transplanted mouse models, each with its distinct advantages and limitations. In chemical-induced models, the carcinogen spontaneously initiates tumor formation through a multistep process. The resemblance of this model to human carcinogenesis renders it an ideal preclinical platform for studying HNSCC initiation and progression from precancerous lesions. The major drawback is that these models are time-consuming and, like human cancer, unpredictable in terms of timing, location, and number of lesions. GEMMs involve transgenic and knockout mice with gene modifications, leading to malignant transformation within a tumor microenvironment that recapitulates tumorigenesis in vivo, including their interaction with the immune system. However, most HNSCC GEMMs exhibit low tumor incidence and limited prognostic significance when translated to clinical studies. Transplanted mouse models are the most widely used in cancer research due to their consistency, availability, and efficiency. Based on the donor and recipient species matching, transplanted mouse models can be divided into xenografts and syngeneic models. In the latter, transplanted cells and host are from the same strain, making syngeneic models relevant to study functional immune system. In this review, we provide a comprehensive summary of the characteristics, establishment methods, and potential applications of these different HNSCC mouse models, aiming to assist researchers in choosing suitable animal models for their research.

AKR1C2 genetic variants mediate tobacco carcinogens metabolism involving bladder cancer susceptibility.

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72-0.97, P = 1.86 × 10-2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10-3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer.

Menthol and filter ventilation in cigarettes: prevalence estimates and relationships with harm perception and smoking exposure.

INTRODUCTION: Menthol and filter ventilation (FV) contribute to cigarette appeal. This observational study examines the US prevalence of menthol versus non-menthol cigarette use by FV and how harm perceptions, cigarettes per day and biomarkers of exposure vary. METHODS: Population Assessment of Tobacco and Health Study (2013-2014) was merged with FV levels of cigarettes and restricted to daily smoking adults who had a usual cigarette variety and did not regularly use other tobacco (N=1614). Weighted descriptive statistics identified the prevalence of menthol and non-menthol use by low (0.02%-10.04%), moderate (10.05%-23.40%), high (23.41%-28.12%) and very high FV (28.13%-61.10%). Weighted linear regression was used to examine differences in outcomes by menthol/FV adjusted for potential confounders. RESULTS: The prevalence of a usual brand that was non-menthol, low FV was the lowest at 2.91%. Using non-menthol cigarettes with high and very high FV (≥23.4%) vs low FV (≤10.04%) was associated with a greater likeliness of misperceiving one's cigarette variety to be less harmful than other varieties (p values<0.05). Total nicotine equivalent, biomarker for nicotine exposure, was elevated (p values<0.05) among three non-menthol groups (low, moderate and very high FV) compared with two menthol groups (moderate, very high FV). CONCLUSION: The well-documented harm misperception linked to higher FV is more apparent in those using non-menthol than menthol cigarettes. Increased exposures were observed among some non-menthol cigarette users compared with some menthol cigarette users. These results should by no means delay a menthol ban but rather motivate concerted public health efforts to accompany the menthol ban to maximise smoking cessation.