Continuous exposure with flux density led to increased nDNA damage exclusively in epithelial cells

A small group of cells involved in the production of cerebrospinal fluid and, notably, in iron transport from blood into the brain interstitium. This iron transport is connected to the production of free radicals via the Fenton reaction. Schmitz et al. therefore hypothesized that MF exposure mainly affects iron transport, potentially causing increased nDNA damage in the affected cells. Accordingly, one could AZ 960 conclude that MF exposure may lead to nDNA damage via the generation of free radicals. However, the question remains open as to whether this effect is present in all brain cells or preferentially in a relatively small group of cells which are involved in iron transport. In the brain, plexus epithelial cells and endothelial cells transport iron into the liquor or the brain. With respect to potential consequences, however, damage related to all cells may be less dangerous in the long run than damage only to a distinct group of cells. In this regard, the epithelial cells of the choroid plexus seem to be of particular importance. These cells are defined as a subtype of macroglia. In addition to CSF production, the choroid plexus acts as a filtration system, removing metabolic waste and excess neurotransmitters from the CSF. Hence, the epithelial cells of the choroid plexus have an important role in helping to maintain the extracellular environment required by the brain to function optimally. The choroid plexus is involved in a variety of neurological disorders, including inflammatory, infectious, neurodegenerative, and neoplastic diseases. For example, amyloid beta accumulates in the choroid plexus in Alzheimer’s disease. Furthermore, choroid plexus papilloma and carcinoma represent the most common brain tumors in the first year of life. A conclusive answer to the question raised above can only be given when methods are used that allow cell type specific analyses in situ. This is not the case when demonstrating DNA strand breaks with the so-called comet-assay, even though this method is very sensitive when used properly. Rather, cell type specific effects can be measured with the following specific autoradiographic methods : in situ nick translation, representing the relative amount of unrepaired nDNA SSB at the time of an animal’s death ; and unscheduled DNA synthesis, demonstrating a preceding nDNA repair. Concerning the sensitivity of these methods, one has to take into account that autoradiographic silver grains seen over a histologic structure are the product of 3 H-radioactivity present in the structure, as well as the exposure time of the autoradiograph. The latter can be increased up to 12 months, provided that very specific technical prerequisites are given. This is due to the fact that the photographic emulsion used in this procedure works linearly over a time interval of 12 months. With an exposure time of 250 days, silver grains produced by less than one beta decay per cell nuclear profile area per day could be reproducibly obtained in previous UDS studies. In the case of ISNT studies, only indirect information regarding sensitivity has been reported: Wang et al. showed a linear relationship between the number of cell nuclear silver grains and dose for some cell lines in vitro after gamma irradiation in the range of 0–1 Gy. It appears feasible that enhanced sensitivity could have been obtained when increasing the exposure time of one day used by the authors of this study. Autoradiographs of UDS studies can also be evaluated with respect to cytoplasmic grain densities, representing mitochondrial DNA synthesis rates at the time of 3 H-TdR application.