Analytical toxicology and clinical applications - Lennart Möller
The research is directed towards human cells and clinical applications. In the Stockholm Particle Group network (KI, KTH, SU) the focus is on nano-structures towards drug delivery or as general exposure of ultrafine particles.
A unique artificial lung is constructed were nano-structures can be generated and transported in a way that a mono-layer of human lung cells will be exposed. The mechanisms, interaction with DNA (lesions) and oxidation (ageing) of DNA are then investigated in vitro under relevant human conditions.
Other components that can damage DNA are antioxidants, for instance vitamins, that easily can shift to act as oxidants. Vitamins A and C can at physiological levels oxidize DNA. This effect can be increased if “minerals” are present. Minerals are often metals that can catalyze oxidative processes. Interestingly, the scientific literature report negative effects (increase of cancer and mortality) of vitamin supplementations in western populations. The best way to take vitamins and antioxidants is to eat fruit and vegetables, then it is impossible to over dose. Further, the artificial antioxidants like vitamin E is one component. In fruit and vegetables there is a mixture of eight varieties of vitamin E. That difference make a difference.
Several diseases have oxidative processes as a key issue and therefore the in vitro data can be applied to animal studies and/or clinical situations. Clinical studies are performed to investigate interactions, optimization of clinical treatments and reduction of oxidative symptoms. Drug developments are ongoing regarding transplantation, prostate disease and inflammatory diseases. Further, clinical studies are investigated by the Comet Assay (50-100 cells are enough) and are applied to kidney disease, environmental exposure and other relevant clinical situations.
A nano-particle cluster (red) that has moved all the way into the nucleus (blue) of a cell where it hits DNA (oxidation, aging of DNA, or DNA strand) breaks. There are only a few papers in the literature that have been able to visualize nano-structures reaching the cell nucleus.