Outdoor air pollution and DNA damage

Short abstract

Commentary on the paper by Tovalin et al (see page 230)

Although working outdoors has frequently been considered more healthful than working indoors, a growing literature suggests that outdoor air exposures increase the risk for a variety of diseases, such as asthma, heart disease, and lung cancer.¹,² Consistent with these epidemiological studies are reports using the ³²P‐postlabelling assay for stable DNA adducts showing that outdoor air causes DNA damage,³ which is a prerequisite for most mutation and cancer. Supporting these observations are hundreds of studies using primarily the Salmonella mutagenicity assay showing that the particulate and volatile fractions of outdoor air are mutagenic.⁴

As reviewed by Tovalin and colleagues⁵ in this issue of OEM, a few studies have used the single cell gel electrophoresis (comet) assay to assess DNA damage associated with outdoor air pollution. However, unlike many of the studies using the ³²P‐postlabelling assay, studies using the comet assay have not included the personal monitoring of pollutants in order to link the DNA damage to specific components of outdoor air. With one exception, these studies have generally examined only those tissues exposed directly to air (epithelia from the nose, tear ducts, or buccal region), and they have not compared DNA damage in people working outdoors to those working indoors.

By incorporating personal monitors into their study, Tovalin and colleagues⁵ have begun to provide a link between the exposure assessment of outdoor air pollutants and systemic DNA damage as measured by the comet assay associated with outdoor air pollution. The authors show that relative to indoor workers, outdoor workers have higher levels of systemic DNA damage that is associated with levels of particulate matter (PM) and 1‐ethyl‐2‐methyl benzene (as measured by personal monitors) and ozone (estimated by modelling).

Gaseous and particulate emissions from sources such as power stations, various industries, and vehicles, along with their atmospheric transformation products, cause damage to public health and to the environment.¹,² In particular, recent prospective studies have confirmed previous findings¹,² by showing that exposure to inhaled (PM₁₀), fine (PM_2.5), and ultra‐fine (PM_0.1) particles in outdoor air is associated with an increased risk for lung cancer.⁶,⁷ Although the levels of ozone in outdoor air also have been associated with an increased risk in lung cancer and DNA damage, the causal nature of this relationship is unclear.⁸,⁹,¹⁰

Tovalin and colleagues provide mechanistic support for these epidemiological observations by showing that the DNA damage in outdoor workers was associated with PM_2.5. This is the first clear demonstration that particles of this size in outdoor air are associated with DNA damage in humans as measured by the comet assay. This emphasises the importance of small particles in outdoor air as the cause of fatal diseases. Small particles are more mutagenic than large particles, and air with a higher concentration of small particles is more mutagenic than is air with larger particles.⁴

Tovalin and colleagues also found an increased level of alkali labile sites in outdoor workers relative to indoor workers. This type of DNA damage is likely due to oxidative stress, consistent with the observed association between DNA damage, PM_2.5, and ozone. Mechanistic studies of DNA damage using the comet assay in cultured human fibroblasts exposed to urban dust particles indicate that the genotoxicity of PM is due to a combination of DNA adduct‐forming polyaromatic compounds, oxidising agents, as well as the insoluble particle core itself.¹¹

The advantages and limitations of the comet assay for human biomonitoring have been discussed.¹² Supporting the use of the assay are the results obtained in the present study, which are consistent with other measures of DNA damage, most notably the ³²P‐postlabelling assay for stable DNA adducts and assays for haemoglobin adducts.³ The use of these and other biomarkers of DNA damage and mutation in studies of outdoor air pollution is critical to understanding the mechanisms by which polluted air leads to human disease.³ A recent statistical analysis of published biomarker studies showed that biomarkers had smaller variance ratios than did air measurements, suggesting that biomarkers would provide a less biasing surrogate for exposure than would typical measurements of chemicals in the air.¹³

The work of Tovalin and colleagues adds to the growing body of data indicating that genotoxic substances in outdoor air result in systemic DNA damage, some of which is likely due to oxidative stress, and highlights the value of biomarkers for assessing responses and exposure to outdoor air pollution. Because the work of Tovalin and colleagues is a small pilot study, the results need to be interpreted cautiously. Nonetheless, further work in this important area should be encouraged and supported.