Effects of environmental air pollution on endogenous oxidative DNA damage in humans.
Epidemiological studies conducted in metropolitan areas have demonstrated that exposure to environmental air pollution is associated with increases in mortality. Carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) are the major source of genotoxic activities of organic mixtures associated with respirable particulate matter, which is a constituent of environmental air pollution. In this study,we wanted to evaluate the relationship between exposure to these genotoxic compounds present in the air and endogenous oxidative DNA damage in three different human populations exposed to varying levels of environmental air pollution. As measures of oxidative DNA damage we have determined 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and cyclic pyrimidopurinone N-1,N(2) malondialdehyde-2'-deoxyguanosine (M(1)dG) by the immunoslot blot assay from lymphocyte DNA of participating individuals. The level of endogenous oxidative DNA damage was significantly increased in individuals exposed to environmental air pollution compared to unexposed individuals from Kosice (8-oxodG adducts) and Sofia (M(1)dG adducts). However, there was no significant difference in the level of endogenous oxidative DNA and exposure to environmental air pollution in individuals from Prague (8-oxodG and M(1)dG adducts) and Kosice (M(1)dG adducts). The average level of M(1)dG adducts was significantly lower in unexposed and exposed individuals from Kosice compared to those from Prague and Sofia. The average level of 8-oxodG adducts was significantly higher in unexposed and exposed individuals from Kosice compared to those from Prague. A significant increasing trend according to the interaction of c-PAHs exposure and smoking status was observed in levels of 8-oxodG adducts in individuals from Kosice. However, no other relationship was observed for M(1)dG and 8-oxodG adduct levels with regard to the smoking status and c-PAH exposure status of the individuals. The conclusion that can be made from this study is that environmental air pollution may alter the endogenous oxidative DNA damage levels in humans but the effect appears to be related to the country where the individuals reside. Genetic polymorphisms of the genes involved in metabolism and detoxification and also differences in the DNA repair capacity and antioxidant status of the individuals could be possible explanations for the variation observed in the level of endogenous oxidative DNA damage for the different populations.
Singh
Rajinder
R
Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, University Road, Leicester LE1 7RH, UK. rs25@le.ac.uk
Kaur
Balvinder
B
Kalina
Ivan
I
Popov
Todor A
TA
Georgieva
Tzveta
T
Garte
Seymour
S
Binkova
Blanka
B
Sram
Radim J
RJ
Taioli
Emanuela
E
Farmer
Peter B
PB
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000393:Air Pollutants / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D016273:Occupational Exposure; D010084:Oxidation-Reduction; D016495:Police; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012907:Smoking
D000393:Air Pollutants; D002274:Carcinogens, Environmental; D011084:Polycyclic Aromatic Hydrocarbons; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine