An approach to investigating the importance of high potency polycyclic aromatic hydrocarbons (PAHs) in the induction of lung cancer by air pollution

Abstract

Evidence suggests that people living in urban areas have an increased risk of lung cancer due to higher levels of air pollution in these areas. Benzo[a]pyrene (B[a]P) is currently used as the main indicator of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in air pollution, but there is concern that B[a]P may not be the ideal surrogate of choice for PAH mixtures since higher potency PAHs have recently been identified which could potentially contribute more and variably to the overall carcinogenicity. Dibenzo[a, h]anthracene (DBA) and dibenzo[a, l]pyrene (DB[a, l]P) are estimated to have carcinogenic potencies 10 or more times greater than B[a]P but data on their presence and formation in the environment are limited. Several occupational and environmental PAH biomonitoring studies are reviewed here, with particular focus on the specific exposure groups, study design, sample tissue, in particular the use of nasal tissues, and biomarkers used in each study. Consideration of these data is then used to propose a novel biomonitoring approach to evaluate exposure, uptake and the role of high potency PAHs in air pollution-related lung cancer. This is based upon an occupational study examining specific DNA adducts for DBA and DB[a, l]P in nasal cells to evaluate the extent to which these high potency PAHs might contribute to the increased risk of developing lung cancer from 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.