Biomakers of genotoxicity of urban air pollution: a dose-response study

Información del proyecto

Identificador del acuerdo de subvención: IC20960063

Proyecto cerrado

Fecha de inicio 1 Noviembre 1996

Fecha de finalización 31 Mayo 1999

Financiado con arreglo a

• Specific research, technological development and demonstration programme in the field of cooperation with third countries and international organizations, 1994-1998

Coste total

Sin datos

Aportación de la UE

Sin datos

Coordinado por

NATIONAL HELLENIC RESEARCH FOUNDATION
Greece

Objetivo

The proposed project involves the investigation of the relationships between various markers of exposure to, early bioiogical effects of, and individual susceptibility to genotoxins present in the urban atmospheric air measured in human populations living in the city of Athens or in a nearby low-pollution area. The study has been designed with strict epidemiological criteria and aims to provide data on dose-response relationships which can be used for the setting of air quality guidelines and for risk assessment:
a) Non-smoking volunteers (120 living in different areas of Athens with levels of air pollution ranging from moderate to among the highest in Europe and 80 living in or near Halkida, a low-pollution area 70 kilometers from Athens) will be studied. The size of the population groups has been determined using power calculations based on the results of a recent pilot study and is considered to allow sufficient statistical power to distinguish between the effects of different degrees of exposure.
b) A battery of state-of-the-art biomarker assays will be employed, including measurements of external exposure to suspended particulates, their associated polycyclic aromatic hydrocarbons and NOx using personal monitors, urinary 1-hydroxypyrene (a measure of the internal dose of polycyclic aromatic hydrocarbons), DNA and protein adducts in lymphocytes, HPRT mutations, sister-chromatid exchanges and chromosome aberrations in lymphocytes, and polymorphisms in carcinogen activating and detoxifying genes as well as in rare Ha-ras alleles. The effects of seasonal variation will be examined by measuring all markers on each individual twice, once in the summer and once in the winter. In addition to biological and environmental monitoring, detailed information will be obtained from each participating individual on time pattern activities, food consumption and other factors of relevance. c) The quantitative relationships between the various markers will be examined by statistical modelling using non-parametric smothing techniques to investigate the existence of thresholds. By focusing on populations derived from relatively close geographical regions of the same country, the effects of confounding factors such as diet and other cultural factors will be minimised. In addition, measurement of urinary cotinine will be employed to control for exposure to environmental tobacco smoke (passive smoking).
d) In addition to already existing, well validated assays, some work towards the development of an assay for protein adducts induced by benzene (a human leukemogen for which concern has been expressed in view of its presence at increasing concentrations in the atmospheric air of European cities) will also be carried out which, if successful, will be applied to the population samples. Furthermore, specimens of the biological samples collected will be stored for future analysis for additional markers of interest.
An important, additional component of the proposed project is a toxicokinetic study of PAH-related biomarkers in volunteers who will be subjected to controled exposure to tobacco smoke, a human carcinogen. The data obtained in this study, in combination with the known cancer risks associated with exposure to tobacco smoke, will be employed to facilitate the conversion of the corresponding biomarker data of the population study into risk estimates. biomarkers; genetic toxicity; risk assessment; molecular epidemiology;

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias químicas › química orgánica › hidrocarburo
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas
• ingeniería y tecnología › ingeniería ambiental › ingeniería de la contaminación atmosférica
• ciencias naturales › ciencias de la tierra y ciencias ambientales conexas › ciencias ambientales › contaminación
• ciencias naturales › ciencias biológicas › genética › cromosoma

Programa(s)

• FP4-INCO - Specific research, technological development and demonstration programme in the field of cooperation with third countries and international organizations, 1994-1998

Tema(s)

• 0102 - Cooperation with the countries of central and eastern Europe and with the new independent states of the former Soviet Union

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

NATIONAL HELLENIC RESEARCH FOUNDATION

• Aportación de la UE: Sin datos
• Dirección: 48,Vas. Constantinou Avenue 48 ; 11635 ATHENS ; Grecia
• Coste total: Sin datos

Participantes (2)

INSTITUTE OF EXPERIMENTAL MEDICINE - ACADEMY OF SCIENCES OF THE CZECH REPUBLIC

Chequia

• Aportación de la UE: Sin datos
• Dirección: Videnska 1083 ; 142 20 PRAHA 4
• Coste total: Sin datos

Prague Institute of Advanced Studies

Chequia

• Aportación de la UE: Sin datos
• Dirección: 366,U Michelského Lesa 366 ; 140 00 Praha 4
• Coste total: Sin datos