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Assessment of human exposure to urban environmental carcinogenic pollutants

Objective

The objective of the project is the development of methods for assessing the genetic burden, resulting from exposure to chemical carcinogens, in the general population.


The genetic burden associated with human exposure to urban air pollution is as yet unclear, although the presence of a wide variety of carcinogenic chemicals has been identified. Exposure to genotoxic carcinogens results in the formation of covalently bound adducts between the carcinogen and DNA. Many so-called 'non-genotoxic' carcinogens also damage DNA by virtue of the fact that they generate active radicals which oxidize nucleic acid bases. Measurement of adducts or oxidized DNA bases may thus be used as a monitor of carcinogen exposure. Exposure to genotoxic carcinogens may also be monitored by determination of adducts formed with proteins, such as haemoglobin.

This research project is concerned predominantly with the development of novel biomonitoring approaches using adduct measurement. These methods are to be applied to biological samples collected from populations in a representative group of European cities and from Kuwaitis exposed to high levels of oil combustion pollutants as well as from populations in Northern and Southern Bohemia. A questionnaire to gather relevant information on lifestyle and environmental factors will be used. Other information to be gathered on the exposed individuals are the analysis of their metabolic phenotype (i.e. capacity to metabolise carcinogens to their active species) and of their DNA repair ability (i.e. capacity to remove genotoxic damage).

The analytical procedures used to detect DNA adducts will be 32P-postlabelling, gas chromatography-mass spectrometry (GC-MS) and HPLC. 32P-postlabelling is an exceptionally sensitive technique capable of detecting carcinogen-modified bases in DNA. It is intended to make several innovations to this method, to make it more amenable for routine use. Oxidative DNA damage (8-hydroxyguanine) will be monitored using HPLC; attempts will also be made to use GC-MS to monitor other oxidized DNA bases, and adducts of genotoxic carcinogens with haemoglobin. Traditionally, lymphocyte DNA is favoured for adduct measurements. It is planned to investigate other DNA sources (e.g. placenta, oral tissues, buccal smears) which may be of greater relevance to carcinogen risk analysis.

The work will result in:

i) The design of novel biomonitoring methods for detecting adducts of carcinogens with DNA and protein,
ii) A comparison of adduct levels in DNA from different tissues which will indicate the most appropriate tissues to use for biomonitoring purposes,
iii) The establishment of baseline data for adducts levels, as a pre-requisite for epidemiological studies at the EC level.

Call for proposal

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Coordinator

MEDICAL RESEARCH COUNCIL
EU contribution
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Address
Lancaster Road University of Leicester Hodgkin Bui
LE1 9HN Leicester
United Kingdom

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Total cost
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Participants (3)