THEME I – Adverse outcome pathways and exposure-response relationships for ionising and non-ionising radiation

Overview

The exposure of humans to electromagnetic radiation is increasingly gaining attention from society at large, who are concerned that such exposures might be a potential cause of ill-health.

Research projects in this Theme address the potential health effects of the most prevalent electromagnetic radiation that humans are exposed to, namely: ionising and non-ionising radiation, sunlight, mobile phone and radio waves. The approaches employed for these different waves are diverse, ranging from cell-based biological investigations to cohort studies and epidemiology.

The outcomes that will be measured are similarly diverse: from effects on cell behaviour and characteristics, to alterations in incidences of illness and pathologies. Collectively, these wide-ranging investigations will provide insights into the potential health impacts of these different types of radiations.

Theme Leads

Theme I Projects

Project 1: Nuclear installations and childhood cancer – PI Bethan Davies (ICL)
Researchers – Bethan Davies (ICL), Paul Elliott (ICL), Fred Piel (ICL) Mireille Toledano (ICL), Daniela Fecht (ICL)
Project outline: As part of ongoing surveillance of nuclear installations in Great Britain, the Committee on Medical Aspects of Radiation in the Environment (COMARE) requested that the UK Small Area Health Statistics Unit (SAHSU) undertake a re-evaluation of childhood cancer near 28 installations following previous reports of an excess cancer risk near nuclear sites. We are using data on incident cases of cancer from 1995-2016 from the UK Health Security Agency (UKHSA) and the Office for National Statistics (ONS) historical data, Welsh Cancer Intelligence & Surveillance Unit (WCISU) and Scottish Information Services Division (ISD).
Overall objectives: We will compare sex-specific annual incident cases and the overall age distributions of cases of childhood cancers (<15 years) around nuclear installations to reference levels, and conduct specific analyses by country and cancer type (Leukaemia and/or non-Hodgkin’s Lymphoma (LNHL), Central Nervous System (CNS) tumours and solid tumours).
Project 2:Ionising radiation adverse outcome pathways for non-cancer disease including circulatory diseases, ageing and cataract – PI Dr Paul O'Mahoney
Researchers – Dr Paul O'Mahoney (UKHSA), Liz Ainsbury (UKHSA), Sylwia Kabacik (UKHSA), Christopher Whiteman (UKHSA); Stephen Barnard (UKHSA)
Project outline: Exposure of the heart to ionising radiation increases the risk of developing cardiovascular disease. Upon irradiation, endothelial cells that constitute the inner lining of the coronary artery, become highly adhesive and less tightly associated with each other. This increases the likelihood that circulating monocytes would be trapped by the sticky surface of the endothelial cells and readily make their way through the more permeable endothelium into the arterial wall, which is a cardinal step in formation of atherosclerotic plaques. These radiation-induced endothelial properties are akin to those that emerge spontaneously with age, raising the question of whether radiation induces ageing and whether age at exposure is an important determinant of adverse outcome (atherosclerotic diseases).
Overall objectives: The aim is to ascertain whether age (17 to 60 years) at time of exposure is a determinant of an adverse outcome of radiation to the coronary artery. Endothelial cells from human coronary artery derived from donors of different ages will be X-irradiated (≥2 Gy) and subjected to functional assays that will measure adhesiveness of their apical surface and permeability of the endothelial layer. These results will inform whether age has an influence on the magnitude of radiation effects on these cells.
Project 3: Health risks associated with mobile phones and police radios – PIs Paul Elliott (ICL), Mireille Toledano (ICL)
Researchers – Paul Elliott (ICL), Mireille Toledano (ICL), Simon Mann (UKHSA), He Gao (ICL), Marzieh Araghi (ICL), Steven Shen (ICL), Joel Heller (ICL)
Project outline: Epidemiological studies on the safety of exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by modern mobile communication devices have found no convincing evidence of adverse health effects, however given their relatively recent introduction and their almost ubiquitous use it is essential to continue investigation of any potential long-term effects.
Overall objectives: The aim of this project is to investigate long-term health effects of RF-EMF exposure in some of the largest worldwide study cohorts of mobile communications users. We will analyse cancer risk and mobile phone use in the international COSMOS study of over 300,000 mobile phone users (100,000 in the UK) and initiate analyses of mobile phone use and cardiovascular disease; we will investigate the longitudinal association between use of mobile phones and other wireless technologies, and cognitive development in the SCAMP cohort of ~6,000 adolescents across Greater London; and we will continue follow up of the Airwave study of the British police forces with a view to further quantifying cancer risk in relation to police radio use.
Project 4: Potential effects of sunlight on cardiometabolic health – PI Dr Paul O'Mahoney
Researchers – Dr Paul O'Mahoney (UKHSA), Liz Ainsbury (UKHSA), Gareth Hazel (UKHSA), Marina Khazova (UKHSA)
Project outline: The adverse health effect (melanoma) resulting from over-exposure to the sun forms the basis of current public health advice, which advocates close to total sun-avoidance. However, an increasing number of emerging reports suggest that sunlight induces hitherto unappreciated health benefits beyond vitamin D synthesis, that could reduce blood pressure, suppress weight gain from consumption of high-fat diets and prevent a range of metabolic disorders. One of the underlying mechanisms is thought to be light-induced production of nitric oxide, which we have characterised to be readily triggered in skin cells by ultraviolet A (UVA). There are also emerging reports that light at longer wavelengths within the visible solar spectrum has beneficial health effects as well. It is now necessary to ascertain the limits of the UVA effect in time and dose, and to explore the potential biological impact of other wavelengths of the solar spectrum.
Overall objectives: To ascertain the duration of nitric oxide production from acute exposure to UVA. To establish an out-door experimental platform to measure the effects of actual solar radiation on DNA damage and nitric oxide production. Following characterisation of UVA-induced production of nitric oxide, we will proceed to study the impact of UVA exposure as a function of time. This is necessary to ascertain the duration of the effect and to assess the likelihood of it having a significant impact on the body. Primary healthy human skin cells will be exposed to UVA light at a dose that is equivalent to 30 minutes of exposure to midday sun in UK in the summer. The production of nitric oxide will be tracked from the point of exposure for up to 5 days. At the same time, we will set-up an experimental platform to measure the impact of actual sunlight (with measured solar doses) on DNA damage as well as nitric oxide production.

Theme I Investigators