Diagnosis, monitoring and prevention of exposure-related non-communicable diseases in the living and working environment: DiMoPEx-project is designed to determine the impacts of environmental exposure on human health

Abstract

The WHO has ranked environmental hazardous exposures in the living and working environment among the top risk factors for chronic disease mortality. Worldwide, about 40 million people die each year from noncommunicable diseases (NCDs) including cancer, diabetes, and chronic cardiovascular, neurological and lung diseases. The exposure to ambient pollution in the living and working environment is exacerbated by individual susceptibilities and lifestyle-driven factors to produce complex and complicated NCD etiologies. Research addressing the links between environmental exposure and disease prevalence is key for prevention of the pandemic increase in NCD morbidity and mortality. However, the long latency, the chronic course of some diseases and the necessity to address cumulative exposures over very long periods does mean that it is often difficult to identify causal environmental exposures. EU-funded COST Action DiMoPEx is developing new concepts for a better understanding of health-environment (including gene-environment) interactions in the etiology of NCDs. The overarching idea is to teach and train scientists and physicians to learn how to include efficient and valid exposure assessments in their research and in their clinical practice in current and future cooperative projects. DiMoPEx partners have identified some of the emerging research needs, which include the lack of evidence-based exposure data and the need for human-equivalent animal models mirroring human lifespan and low-dose cumulative exposures. Utilizing an interdisciplinary approach incorporating seven working groups, DiMoPEx will focus on aspects of air pollution with particulate matter including dust and fibers and on exposure to low doses of solvents and sensitizing agents. Biomarkers of early exposure and their associated effects as indicators of disease-derived information will be tested and standardized within individual projects. Risks arising from some NCDs, like pneumoconioses, cancers and allergies, are predictable and preventable. Consequently, preventative action could lead to decreasing disease morbidity and mortality for many of the NCDs that are of major public concern. DiMoPEx plans to catalyze and stimulate interaction of scientists with policy-makers in attacking these exposure-related diseases.

Keywords: Environmental/occupational exposure to xenobiotics; Human biomonitoring; Noncommunicable diseases.

Fig. 1

The wide spectrum of sources needed to ensure accurate exposure assessment

Fig. 2

Quantitative estimation of the exposure performed by a direct or indirect approach; example from the occupational medicine

Fig. 3

New study protocols needed for animal models. Animal models for carcinogenicity bioassays: Hazard identification: carcinogenic effects may be observed later than 112 weeks after xylene exposure

Fig. 4

Sources of nucleic acids and NCDs

Fig. 5

Application of MN assay in human biomonitoring (effect monitoring) after environmental and occupational exposures

Fig. 6

Human biomonitoring: how a specific biomarker can serve as specific aim in a study design. The “meet-in-the-middle” principle to show how biomarkers can be used prospectively to contribute to human health risk assessment and retrospectively in population-based studies to identify molecules for suitability as intermediate biomarkers of “‘early effect”effect’ to link exposure biomarkers with disease endpoints

Fig. 7

Potential sources of ROS formation in particle- exposed cells. Note: interpreting the effects of antioxidants on cellular responses from particle exposure is inherently difficult due to the many potential sources of ROS. ROS may be generated directly by reactive particle surfaces in contact with aqueous media, soluble organic constituents such as PAHs and quinones may form ROS and reactive electrophilic metabolites through redox cycling and metabolic activation, Fenton-reactive transition metals may contribute to formation of highly reactive hydroxyl radicals (●OH), activation of intracellular signaling pathways may trigger production of superoxide (O₂●-) and hydrogen peroxide (H₂O₂) through activation of membrane bound oxidases, and damage to mitochondria may lead to superoxide production. The figure has previously been published in [95]