Linking exposure to environmental pollutants with biological effects

https://doi.org/10.1016/j.mrrev.2003.06.010Get rights and content

Abstract

Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene, metabolism and inflammation.

By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual exposure to PM2.5, nitrogen dioxide (NO2) and benzene has been measured in groups of 40–50 subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1).

With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion. With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM2.5 exposure. Several types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand breaks and 8-oxodG in lymphocytes increased significantly in the summer period, requiring control of confounders. Similar seasonal effects on strand breaks and expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported.

In the present setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM2.5, use of GPS, as well as genomics and proteomics based biomarkers.

Introduction

Numerous epidemiological studies have shown an increased morbidity and mortality due to ambient air pollution [1], [2]. Ambient air contains a complex mixture of toxics, including particulate matter (PM), irritant gases and benzene. PM is the component of air pollution believed to be responsible for many of these adverse health effects, and several studies have shown a positive association between overall daily mortality and ambient particle concentrations [1]. Long-term exposure to high particle levels increase risk of cancer, respiratory diseases and arteriosclerosis, whereas short-term exposure-peaks cause exacerbation of bronchitis, asthma and other respiratory diseases as well as changes in heart rate variability [2], [3], [4]. The size fraction of PM may have different effects, i.e. PM2.5 and particularly ultrafine PM may be more potent than coarse PM. Carcinogenic effects of PM may relate both to the content of PAH and oxidative damage to DNA generated by transition metals, benzene, metabolism and/or inflammation. However, at low concentrations exposure assessment and establishing relationships with biological effects may be difficult. By means of monitors of individual exposure to air pollutants and of biomarkers of internal dose, biologically effective dose and early biologically effect as well as markers of individual susceptibility, such relationships may be documented (Fig. 1).

Section snippets

Measuring personal exposure to particles

Almost all studies of particle-related adverse health effects have relied upon urban background measurements as a surrogate for exposure of all individuals in a population. However, people spend around 90% of their time indoors [5], and it is widely recognized that a significant proportion of personal exposure to particles occurs in indoor environments. Therefore, a more detailed and systematic knowledge of personal exposure will improve the ability to estimate personal exposure in future

Biomarkers of internal dose and air pollutants

Measurement of personal exposure to particles and other ambient air toxics in relation to adverse health effect may be difficult. However, by means of biomarkers mechanistically related to the relevant health effect it may be possible to assess relevant exposure to particulate matter and the involved sources (Fig. 1). A biomarker should be sensitive and specific to only the source of exposure examined but unfortunately this is very rarely the case.

A biomarker of internal dose is an exposure

Biomarkers of biologically effective dose and effects

The exact mechanisms whereby particles exert their toxic effects at the cellular level are not fully understood. Several hypotheses have been suggested, a schematic overview of which is presented in Fig. 2.

Susceptibility

A considerable inter-individual variability in response to many xenobiotics, has been found and in inhalation toxicology there is a growing interest in the importance of susceptibility, especially related to particles. In epidemiological studies investigating exposure to particulate matter, findings have been driven largely by effects observed in presumed susceptible subpopulations including the aged, especially those with underlying cardiopulmonary diseases, and children with asthma [2].

Conclusion

The overall epidemiological evidence is consistent with the hypothesis that particulate air pollution is an important risk factor in cardiopulmonary disease and mortality even at low levels of exposure. The biological linkages are not fully understood, although the research to date point to an involvement of oxidative stress and inflammation. The use of biomarkers together with careful individual exposure monitoring has been shown to be important tools in gaining insight into these mechanisms.

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