DNA damage and cytotoxicity in type II lung epithelial (A549) cell cultures after exposure to diesel exhaust and urban street particles

All of the particles generated strand breaks and oxidized purines in A549 lung epithelial cells in a dose-dependent manner and there were no overt differences in their potency. The exposures also yielded dose-dependent increase of cytotoxicity (as lactate dehydrogenase release) and reduced colony forming ability with slightly stronger cytotoxicity of SRM1650 than of the other particles. In contrast, only the authentic street particles were able to generate 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in calf thymus DNA, which might be due to the much higher level of transition metals.Authentic street particles and SRMs differ in their ability to oxidize DNA in a cell-free environment, whereas cell culture experiments indicate that the particle preparations elicit a similar alteration of the level of DNA damage and small differences in cytotoxicity. Although it cannot be ruled out that SRMs and authentic street particles might elicit different effects in animal experimental models, this study indicates that on the cellular level, SRM1650 and SRM2975 are suitable surrogate samples for the study of authentic street particles.The hazardous effects related to genotoxicity and cytotoxicity of particulate matter (PM) has been investigated in various cell culture experiments. Oxidative stress due to transition metals and particle-induced inflammation are believed to be important determinants for the generation of DNA damage such as strand breaks (SB) and oxidative damage to the DNA [1]. The 8-oxoguanine base lesion is generated in DNA during oxidative stress, and the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) nucleotide is premutagenic if not repaired prior to DNA replication [2]. The level of oxidized guanine lesions can be measured by chromatographic techniques, antibody-based methods, and enzymatically recognized by e.g. the formamidopyrimidine DNA glycosylase (FPG) of E. coli [3,4]. There is evidence that exposure to urban air pollution increases the level of FPG si