An approach to investigating the importance of high potency polycyclic aromatic hydrocarbons (PAHs) in the induction of lung cancer by air pollution
Introduction
A number of epidemiological studies have indicated that people living in urban areas have an increased (cigarette smoking-adjusted) risk of developing lung cancer compared to people living in rural areas (Hemminki and Pershagen, 1994). A major difference between such environments is the level of air pollution, particularly particulate matter (Motallebi et al., 2003). Recently the increased risk of lung cancer mortality from exposure to particulate air pollution was estimated to be 8% (Pope et al., 2002). Since environmentally polluted atmospheres contain a range of genotoxic substances, the carcinogenic potential of various environmentally relevant matrices such as coal combustion effluents, vehicle exhaust, used motor lubricating oil and sidestream tobacco smoke has been extensively studied in experimental animals. It has been suggested that polycyclic aromatic hydrocarbons (PAHs) present in these mixtures are mainly responsible for their carcinogenic effects (Grimmer, 1991; WHO, 1998).
There is good epidemiological evidence to suggest that several occupational groups with potential exposures to complex mixtures containing PAHs are at significantly increased risk of developing lung cancer. These include coke oven workers, road workers, creosoters, roofers and aluminium smelter workers (Talaska et al., 1996). A correlation between high occupational exposures to mixtures containing PAHs and subsequent cancer development has been reported in many studies (Department of Environment, Transport and the Regions, 1999), and so various countries have proposed targets for carcinogenic air pollutants in order to fulfil national objectives for the reduction of harmful emissions to ambient air.
For practical reasons benzo(a)pyrene (B[a]P) has traditionally been the surrogate marker of choice for measuring ambient exposure to PAH mixtures. For example in the UK, the Expert Panel on Air Quality Standards recommended an Air Quality Standard for PAHs of 0.25 ng/m3 B[a]P as an annual average (Department of Environment, Transport and the Regions, 1999). However, the suitability of B[a]P as an indicator of carcinogenic PAHs has recently been questioned by new findings on the presence of more potent PAHs such as dibenzo[a, l]pyrene (DB[a, l]P) (Pufelete et al., 2004). Given that the relative contributions of these more potent PAHs in ambient air have not been adequately evaluated and there are only limited data on their presence and formation in ambient air, it is possible that their relative contribution to the carcinogenic activity of a total PAH mixture is far greater than that of B[a]P, and suggests further work is required to investigate the potential role of high potency PAHs in air pollution related lung cancer. However, it is neither practical nor feasible to use cancer as an endpoint, as exposures are mixed, and any such study would have to be very large to ensure adequate power. Hence, there is a need for a suitable biomarker to serve as a surrogate for tumourigenicity to help address this question.
This paper considers an approach to providing information that will help enable the significance of newly recognised high potency PAHs in air pollution to be understood with respect to lung cancer induction.
The current knowledge on the relative potency of these compounds is briefly considered below, before the proposals for further work are discussed.
Section snippets
Carcinogenicity of PAHs
Only limited data are available on the potency of specific PAHs to induce lung cancer following exposure by inhalation. The bulk of the animal data is derived from studies that have used routes other than inhalation and/or examined the development of other tumours such as skin carcinomas following dermal contact (WHO, 1998). Carcinogenic potency has been shown in many PAH carcinogenicity studies to vary according to the route of exposure. This is largely due to tissue-related differences in
A new approach to investigate the potential importance of the highly potent PAHs in air pollution in lung cancer induction
Investigating the significance of specific PAHs in air pollution related lung cancer is very difficult. This is because environmental exposures to PAHs tend to be very low and many potential confounding sources of PAHs are known to exist (e.g. diet and environmental tobacco exposure (ETS), including seasonal variations in air levels). Therefore, the use of biomarkers is very important as they can help to reduce misclassification of exposure, provide information on uptake and early biological
Proposed study
Studies in mice using PAHs have established a relationship between DNA adduction in target tissue and carcinogenic potency (Ross et al., 1995; Nesnow et al., 1998). For most PAHs, there is a direct relationship between the extent of DNA adduction and carcinogenic outcome. However, in the case of DBA, the nature of the adduct, derived from the bis-diol epoxide, is such that it appears to be more promutagenic. Hence the relationship between level of adduction and carcinogenicity is steeper than
Acknowledgement
The authors are grateful for advice and comments from members of the Committee of Carcinogenicity of Chemicals in Foods, Consumer Products and the Environment (COC), Dr Heather Walton from the Air Pollution Unit, Department of Health, England, and Professor Donald Davies, Section on Experimental Medicine & Toxicology, Imperial College.
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