CDNP and genotoxicity

- Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure

The genotoxic properties of various particle types has been the focus of several studies concerned with elucidating the role such properties play in particle-associated pathogenicity [34]. However, the mechanisms involved in particle-induced genotoxicity remain poorly understood as particles are uniquely complex compared with soluble genotoxic/carcinogenic compounds, due to their physical and chemical characteristics [125]. There is evidence that 3 of the 4 CDNP studied in this review (diesel, NPCB and welding fume) are carcinogenic in humans or rats [20,38,126,127]. As mentioned earlier, DEP consist of a carbon core with adsorbed PAHs, quinones and transition metals. Genotoxicity, may therefore be caused by the direct (primary) interaction of PAHs which are known to cause DNA adduct formation [128] or alternatively via DNA strand breakage due to the production of reactive oxygen species generated by associated transition metals [8]. Carbon black particles are generally almost free of adsorbed organic compounds; however they have been shown to produce lung tumours in rats following chronic inhalation and instillation studies [127,129]. This indirect (secondary) genotoxicity pathway involves the phenomenon of lung particle overload resulting in a chronic inflammation and hence excessive ROS production leading to DNA damage. Studies by Knaapen et al, have demonstrated that co-incubation of rat lung epithelial cells with activated neutrophils in vitro stimulate the formation of the oxidative DNA lesion 8-OH-dG [32]. Less research has been carried out on the genotoxic effects of welding fumes. Some of the major components of welding fumes include iron, manganese, chromium and in particular hexavalent chromium (Cr^VI) chromium which has been shown to increase levels of 8-OH-dG in rats after inhalation exposure [130]. Yu and co-workers showed that rats exposed for 30 days to manual metal arc stainless steel (MMA-SS) welding fumes, exhibited increased DNA damage as measured by the comet assay and immunohistochemistry for 8-OH-dG [131]. Studies investigating the genotoxic capacity of coal fly ash have shown a role for particulate size and iron release leading to radical generation and oxidative DNA damage [132,133] as well as increased sister-chromatid exchange (SCE) frequencies in peripheral blood lymphocytes from workers occupationally exposed to coal fly ash [134].