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Johannes Kleemann,* Gabi Reichenbach,* Nadja Zöller, Manuel Jäger, Roland Kaufmann, Markus Meissner, Stefan Kippenberger Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany*These authors contributed equally to this workCorrespondence: Stefan KippenbergerDepartment Of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, Frankfurt/Main D-60590, GermanyEmail kippenberger@em.uni-frankfurt.dePurpose: Although regular water is composed of two hydrogens and one oxygen, referred to as H2O, a small amount of water on this planet contains alternative forms of elements with different molecular weights because of the addition of neutrons. The present study was dedicated to studying the effect of heavy water (D2O), in which the two hydrogens become substituted by deuterium, on the cell physiology of different human cells with particular focus on malignant melanoma cells.Methods: Cells were cultured in regular medium in which the content of H2O was gradually substituted by D2O or deuterium-depleted water (DDW). Following this, the changes of basic cellular parameters, such as morphology, migration, proliferation, cell cycle, apoptosis and microtubule integrity were examined.Results: It was found that raising the D2O content above the standard levels led to a concentration-dependent decrease in proliferation. Lowering the D2O levels below this level had no effect. Likewise, elevated D2O levels hampered migration. Moreover, cell-cycle analysis showed an increase of sub-G1 cells. Corroboratively, markers for apoptosis were induced (histone-associated DNA fragments, Bax, and PARP). In regard to microtubule integrity, only very high levels of D2O (75%) caused partial filament condensation.Conclusion: D2O, although chemically identical with H2O, shows proapoptotic and antiproliferative effects on melanoma cells. These findings give a closer look of this interesting compound.Keywords: deuterium oxide, heavy water, melanoma, apoptosis, isotypes