Abstract
Polycyclic aromatic hydrocarbons (PAHs) appear to be significant contributors to the genotoxicity and carcinogenicity of air pollution present in the urban environment for humans. Populations exposed to environmental air pollution show increased levels of PAH DNA adducts and it has been postulated that another contributing cause of carcinogenicity by environmental air pollution may be the production of reactive oxygen species following oxidative stress leading to oxidative DNA damage. The antioxidant status as well as the genetic profile of an individual should in theory govern the amount of protection afforded against the deleterious effects associated with exposure to environmental air pollution. In this study we investigated the formation of total PAH (bulky) and B[ a]P DNA adducts following exposure of individuals to environmental air pollution in three metropolitan cities and the effect on endogenously derived oxidative DNA damage. Furthermore, the influence of antioxidant status (vitamin levels) and genetic susceptibility of individuals with regard to DNA damage was also investigated. There was no significant correlation for individuals between the levels of vitamin A, vitamin E, vitamin C and folate with M 1dG and 8-oxodG adducts as well as M 1dG adducts with total PAH (bulky) or B[ a]P DNA adducts. The interesting finding from this study was the significant negative correlation between the level of 8-oxodG adducts and the level of total PAH (bulky) and B[ a]P DNA adducts implying that the repair of oxidative DNA damage may be enhanced. This correlation was most significant for those individuals that were non smokers or those unexposed to environmental air pollution. Furthermore the significant inverse correlation between 8-oxodG and B[ a]P DNA adducts was confined to individuals carrying the wild type genotype for both the GSTM1 and the GSTT1 gene (separately and interacting). This effect was not observed for individuals carrying the null variant.
Highlights
There is evidence that populations exposed to urban pollution show increased levels of polycyclic aromatic hydrocarbon (PAH) DNA adducts, supporting the hypothesis that Polycyclic aromatic hydrocarbons (PAHs) are significant contributors to the genotoxicity and carcinogenicity of air pollution in the urban environment [1], [2] and [3]
The correlation between 8-oxodG and B[a]P DNA adducts is strongly influenced by genetic susceptibility: individuals carrying the wild type genotype for both the GSTM1 and the GSTT1 gene show a significant strong inverse correlation between the two adducts, while this effect disappears in individuals carrying the null variant
It has been postulated that another contributing cause of carcinogenicity by environmental air pollution may be the production of reactive oxygen species (ROS) following oxidative stress leading to oxidative DNA damage
Summary
There is evidence that populations exposed to urban pollution show increased levels of polycyclic aromatic hydrocarbon (PAH) DNA adducts, supporting the hypothesis that PAHs are significant contributors to the genotoxicity and carcinogenicity of air pollution in the urban environment [1], [2] and [3]. For example, no relationship was found between exposure to particle-bound PAHs and DNA adduct formation when two populations in Greece were compared, and exposure to environmental tobacco was proposed as a more significant determinant of DNA damage [8].The explanation of this finding may be due to the lower levels of PAHs observed in Greece compared to the Czech Republic or Poland. Exposure to respirable particulate matter (PM) has been shown to induce production of ROS [9] and increase levels of 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) in vitro and in vivo in experimental systems (reviewed in Risom et al and Sorensen et al [10] and [11]). A significant relationship has been observed between 8-oxodG adducts in lungs induced by diesel exhaust particles (DEP) and lung tumour incidence in mice [13]
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