Molecular epidemiological approaches to the study of the genotoxic effectsof urban air pollution

Direct epidemiological observations suggest that exposure to high levels of urban air pollution may result in increased risk of lung cancer, sufficien t to account for a few (similar to 1-3) percent of total lung cancer incide nce. Extrapolation from occupational exposure and risk data suggests that a mong potential carcinogens present in polluted urban air, polycyclic aromat ic hydrocarbons (PAHs) may make a major contribution to air pollution-assoc iated lung cancer risks. The use of biomarkers of genotoxocity in large-sca le population studies may help to reduce the uncertainty involved in the as sessment of such risks, especially those associated with relatively low pol lution levels such as nowadays found in many Western cities. Increases in b iomarkers of exposure to urban air PAHs as well as biomarkers of early effe cts have been detected in situations of relatively high levels of air pollu tion (e.g., ambient PAH concentrations of the order of a few tens of microg rams per cubic meter). Evidence has also been found about the modulation ge netic damage accumulation in different individuals by polymorphisms in gene s involved in the activation or detoxification of PAHs, especially of polym orphisms GSTM1 and CYP1A1 genes. However, the inconsistencies in the curren tly reported effects of genetic polymorphisms suggest that additional facto rs may also be important in the modulation of individual susceptibility to the accumulation of PAM-derived genetic damage. Biomarkers studies in popul ations exposed to relatively low ambient PAH concentrations (below 20 mu g/ m(3)) have not demonstrated clear dose-related effects (e.g., on DNA adduct levels), possibly because of the existence of multiple sources and routes of human exposure to PAHs in addition to inhalation of urban air (including , for example, home heating, environmental tobacco smoke and diet), and the consequent difficulty of adequately and specifically assessing atmospheric air-related exposure. This makes it imperative that molecular epidemiology studies be designed in such a way as to allow adequate assessment of expos ure to urban air PAHs at the individual level and over short-, medium- and long-term time periods which correspond to the expression times of differen t biomarkers. (C) 1999 Elsevier Science B.V. All rights reserved.