A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer.

Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.

Hair-Derived Exposome Exploration of Cardiometabolic Health: Piloting a Bayesian Multitrait Variable Selection Approach.

Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status.

Exposure to endocrine disrupting chemicals from beverage packaging materials and risk assessment for consumers.

This study investigated the influence of beverage packaging materials on the presence of endocrine disrupting chemicals (EDCs) in plastic, glass, carton, aluminium, and tin canned non-alcoholic beverages. Results showed that 63 EDCs including perfluoroalkyl and polyfluoroalkyl substances (PFAS), bisphenols, parabens, benzophenone-type UV-filters, biocides, nitrophenols, and alkylphenols, were detected in 144/162 screened products. Detected ∑EDC concentrations ranged from 1.

Metabolomic Signatures of Exposure to Nitrate and Trihalomethanes in Drinking Water and Colorectal Cancer Risk in a Spanish Multicentric Study (MCC-Spain).

We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation.

A software-assisted untargeted liquid chromatography-mass spectrometry method for lipidomic profiling of human plasma samples.

Introduction: In this paper, an analytical pipeline designed for untargeted lipidomic profiling in human plasma is proposed. The analytical pipeline was developed for case-control studies nested in prospective cohorts.

Methods: The procedure consisted of isopropanol protein precipitation followed by reverse phase liquid chromatography coupled to high resolution mass spectrometry and software-assisted data processing.

Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking.

Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case-control studies, using (LASSO)-penalised regression.

UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling.

To adapt in an ever-changing environment, cells must integrate physical and chemical signals and translate them into biological meaningful information through complex signaling pathways. By combining lipidomic and proteomic approaches with functional analysis, we have shown that ubiquitin domain-containing protein 1 (UBTD1) plays a crucial role in both the epidermal growth factor receptor (EGFR) self-phosphorylation and its lysosomal degradation. On the one hand, by modulating the cellular level of ceramides through N-acylsphingosine amidohydrolase 1 (ASAH1) ubiquitination, UBTD1 controls the ligand-independent phosphorylation of EGFR.

Occurrence and fate of legacy and novel per- and polyfluoroalkyl substances (PFASs) in freshwater after an industrial fire of unknown chemical stockpiles.

An industrial warehouse illegally storing a large quantity of unknown chemical and industrial waste ignited in an urban area in Melbourne, Australia. The multiday fire required firefighters to use large amounts of fluorine-free foam that carried contaminated firewater runoff into an adjacent freshwater creek. In this study, the occurrence and fate of 42 per- and polyfluoroalkyl substances (PFASs) was determined from triplicate surface water samples (n = 45) from five locations (upstream, point-source, downstream; 8 km) over three sampling campaigns from 2018 to 2020.

Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer.

Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only).

What is new in the exposome?

The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime. It encompasses also "psychosocial components" including the impact of social relations and socio-economic position on health. In this review we provide examples of recent contributions from exposome research, where we believe their application will be of the greatest value for moving forward.

Cys34 Adductomics Links Colorectal Cancer with the Gut Microbiota and Redox Biology.

Chronic inflammation is an established risk factor for colorectal cancer. To study reactive products of gut inflammation and redox signaling on colorectal cancer development, we used untargeted adductomics to detect adduct features in prediagnostic serum from the EPIC Italy cohort. We focused on modifications to Cys34 in human serum albumin, which is responsible for scavenging small reactive electrophiles that might initiate cancers.

Agnostic Cys34-albumin adductomics and DNA methylation: Implication of N-acetylcysteine in lung carcinogenesis years before diagnosis.

Although smoking and oxidative stress are known contributors to lung carcinogenesis, their mechanisms of action remain poorly understood. To shed light into these mechanisms, we applied a novel approach using Cys34-adductomics in a lung cancer nested case-control study (n = 212). Adductomics profiles were integrated with DNA-methylation data at established smoking-related CpG sites measured in the same individuals.

Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study.

Exposure to air pollution can have both short-term and long-term effects on health. However, the relationships between specific pollutants and their effects can be obscured by characteristics of both the pollution and the exposed population. One way of elucidating the relationships is to link exposures and internal changes at the level of the individual.

Cys34 Adductomes Differ between Patients with Chronic Lung or Heart Disease and Healthy Controls in Central London.

Oxidative stress generates reactive species that modify proteins, deplete antioxidant defenses, and contribute to chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD). To determine whether protein modifications differ between COPD or IHD patients and healthy subjects, we performed untargeted analysis of adducts at the Cys34 locus of human serum albumin (HSA). Biospecimens were obtained from nonsmoking participants from London, U.

Management strategies for trace organic chemicals in water - A review of international approaches.

To ensure an appropriate management of potential health risks and uncertainties from the release of trace organic chemicals (TOrCs) into the aqueous environment, many countries have evaluated and implemented strategies to manage TOrCs. The aim of this study was to evaluate existing management strategies for TOrCs in different countries to derive and compare underlying core principles and paradigms and to develop suggestions for more holistic management strategies to protect the environment and drinking water supplies from the discharge of undesired TOrCs. The strategies in different industrial countries were summarized and subsequently compared with regards to three particular questions: 1) Do the approaches different countries have implemented manage all or only specific portions of the universe of chemicals; 2) What implementation and compliance strategies are used to manage aquatic and human health risk and what are their pros and cons; and 3) How are site-specific watershed differences being addressed? While management strategies of the different countries target similar TOrCs, the programs differ in several important aspects, including underlying principles, the balance between aquatic or human health protection, implementation methods, and financing mechanisms used to fund regulatory programs.

Evaluation of the immunomodulatory effects of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in C57BL/6 mice.

2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate was designed to replace perfluorooctanoic acid (PFOA), which has been mostly phased out of U.S. production due to environmental persistence, detectable human and wildlife serum concentrations, and reports of systemic toxicity.

Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach.

Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers.

Transformation of polyfluorinated compounds in natural waters by advanced oxidation processes.

The presence of perfluorocarboxylic acids (PFCAs) in source and finished drinking waters is a concern with studies showing bioaccumulation and adverse toxicological effects in wildlife and potentially humans. Per/Polyfluoroalkyl substances (PFAS) such as fluorotelomer alcohols have been identified as precursors for PFCAs in biological pathways. In this study, we investigated the fate of 6:2 and 8:2 homologues of the fluorotelomer unsaturated carboxylic acids (FTUCAs) during advanced oxidation process (AOPs).

Identification of Novel Perfluoroalkyl Ether Carboxylic Acids (PFECAs) and Sulfonic Acids (PFESAs) in Natural Waters Using Accurate Mass Time-of-Flight Mass Spectrometry (TOFMS).

Recent scientific scrutiny and concerns over exposure, toxicity, and risk have led to international regulatory efforts resulting in the reduction or elimination of certain perfluorinated compounds from various products and waste streams. Some manufacturers have started producing shorter chain per- and polyfluorinated compounds to try to reduce the potential for bioaccumulation in humans and wildlife. Some of these new compounds contain central ether oxygens or other minor modifications of traditional perfluorinated structures.

Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study.

Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure.

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development.

Chemical and toxicological assessment of a full-scale biosolid compost.

The impact of a full-scale biosolid composting plant on the fate of a broad range of priority organic pollutants was investigated. Chemical analysis was performed at different steps of the process during two seasons. Simultaneously, the toxicological quality was assessed using estrogen α-, dioxin-, and pregnane X-receptor reporter cell lines.