Transplacental carcinogenic mechanisms of black carbon exposure (T-CAB) (R-10234)

Ambient air pollution, including black carbon (BC), entails a serious public health risk because of its carcinogenic potential. Despite the respiratory system being the predominant entry route of particulate air pollution, various studies have indisputably demonstrated associations with a wide range of non-pulmonary health effects. A plausible explanation comprises particles translocation from the lungs into the circulation from which they deposit in distant organs and induce pathology. Recently, we confirmed the hypothesis of translocation from the system to urine. Accordingly, particle translocation may occur from mother to fetus resulting in detrimental predisposition in early life leading later to adverse health outcomes. The general process, known as biological embedding, is central to the developmental origins of health and disease (DOHaD) concept. In the proposed research project, T-CAB, we study the mechanisms of the "hallmarks of cancer" in the DOHaD hypothesis as there remains a need to define how early life exposures can become biologically embedded and may drive carcinogenic processes in later life. Hence, we examine mechanistic pathways and questions about DNA methylation (as well as other molecular targets) associated with the exposure to the environmental stressor black carbon. More specifically, in T-CAB we establish longitudinal evidence about the persistence of alterations from birth to early childhood to understand the kinetics of the hallmarks of carcinogenesis in association with the living environment. In addition, we focus on the same mechanisms in adulthood to establish age-specific insights. T-CAB develops in this way cost-effective policies to pinpoint an optimally healthy environment that can mitigate or reverse epigenetic changes by gathering knowledge in early molecular targets tailored to potential early risks and to understand better individual exposure by measuring the internal black carbon load. If prenatal exposure to BC is associated with important hallmarks of carcinogenesis, this will create novel targets for public health preventive actions and will hopefully trigger environmental health policy to establish guidelines that will be protective for the most susceptible period in life.

Keywords:Ambient air pollution, Black Carbon, Carcinogens

Disciplines:Biophysics not elsewhere classified, Epidemiology