Synergistic Toxicity of Depleted Uranium and UVB Light in Human Skin Cells

Most research addresses uranium-induced cancer through its radiological modes of action, ignoring its chemical reactivity. Lung and kidneys are known target organs for uranium toxicity, but its effects in other organs or tissues are less well understood. It is known that uranium(VI) is photoactivated by UVB-light to form uranium(V) and reactive oxygen species. We therefore hypothesize that combined exposures of uranium and UVB-light may be more toxic to skin than individual exposures. We are testing this hypothesis by exposing cultured human keratinocyte skin cells to depleted uranium in the presence and absence of UVB-light and measuring the effect of these treatments on cell survival. First, the cytotoxicity of two forms of depleted uranium, uranyl acetate (UA) and uranyl nitrate (UN), was tested. We did not find statistically significant differences between UA and UN cytotoxicity (p>0.05). Then, we tested if there is a cytotoxic synergistic effect when combining UA and UVB-light at different doses. Combined exposures to 100 µM UA + 6.6 mJ/cm² and 200 µM UA + 6.6 mJ/cm² were significantly more cytotoxic than an additive response (34% vs. 49% expected and 32% vs. 46% expected, respectively) by Student’s t-test. Additionally, we analyzed cell morphology changes induced by UA alone, UVB alone, and both factors combined using transmission electron microscopy (TEM). UA-dosed samples showed high content of vacuoles with enclosed particles. Results from this work may provide data to expand the focus of uranium toxicity from lung and kidney to include skin as a target organ for carcinogenesis.