Cell type-specific differences in redox regulation and proliferation after low UVA doses

Abstract

21Ultraviolet A (UVA) radiation is harmful for living organisms but in low doses may 22 stimulate cell proliferation. Our aim was to examine the relationships between exposure 23 to different low UVA doses, cellular proliferation, and changes in cellular reactive 24 oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells 25 exposed to UVA doses comparable to environmental, the highest doses (30-50 kJ/m 2 ) 26 reduced clonogenic potential but some lower doses (1 and 10 kJ/m 2 ) induced 27 proliferation. This effect was cell type and dose specific. In both cell lines the levels of 28 reactive oxygen species and nitric oxide fluctuated with dynamics which were 29 influenced differently by UVA; in Me45 cells decreased proliferation accompanied the 30 changes in the dynamics of H 2 O 2 while in HCT116 cells those of superoxide. Genes 31 coding for proteins engaged in redox systems were expressed differently in each cell 32 line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed 33 higher expression in HCT116 cells whereas those for glutathione transferases and 34 copper chaperone were more abundant in Me45 cells. We conclude that these two cell 35 types utilize different pathways for regulating their redox status. Many mechanisms 36 engaged in maintaining cellular redox balance have been described. Here we show that 37 the different cellular responses to a stimulus such as a specific dose of UVA may be 38 consequences of the use of different redox control pathways. Assays of superoxide and 39 hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of 40 cellular redox regulation and help in understanding responses to stressing factors. 41 42 43 44 Ciesielska 3 45 46 48with a wavelength of 100-400 nm, invisible to human sight. The sun is a natural emitter 49 of UV divided into three main fractions UVA (315-400 nm), UVB (280-315 nm), and 50 UVC (100-280 nm), but most of this radiation is blocked by the atmosphere (1,2). UVA 51 constitutes the largest part (∼95%) of UV radiation that reaches the Earth's surface (3), 52whereas UVB represents only 4-5% (1). In irradiated humans UVA reaches the dermis 53 and hypodermis and has no direct impact on DNA, but it can influence cellular 54 structures indirectly by induction of reactive oxygen species (ROS) which can damage 55 macromolecules (4,1). For a long time UV was regarded as damaging for cells and 56 organisms (5), but since a few decades it is known that low doses can also stimulate 57 proliferation of cells; however, the mechanisms underlying this phenomenon are not 58 completely understood (3,1,6,7). 59Studies of signaling pathways in conditions where UVA stimulates cell proliferation 60 show changes in the levels of proteins engaged in controlling proliferation such as 61 cyclin D1 (8,9), Pin1 (3), and Kin17 (10) or activation of epidermal growth factor 62 receptor (EGFR) which is strongly mitogenic in many cell types (8). Experiments on 63 mice showed that UVA can accelerate tumor growth ...

Circuits Regulating Superoxide and Nitric Oxide Production and Neutralization in Different Cell Types: Expression of Participating Genes and Changes Induced by Ionizing Radiation

“…Our analyses of the levels of reactive oxygen and nitrogen species in cells exposed to UV or ionizing radiation showed that these treatments may significantly change the redox conditions and proliferation of cells [ 19 , 47 ]. Thus, in further work, we analyzed the ionizing radiation-induced changes in the expression of genes related to the pathways responsible for the regulation of O 2 • − and NO levels in three cell lines originating from different tissues.…”