Likewise, D2O-induced anti-proliferative effects observed by us in A375 malignant melanoma cells in vitro and in vivo (including M-phase depletion (Figure 1D), CDKN1A upregulation (Figure 4A and Figure 5G), and Ki67 downregulation (Figure 5G)) might be attributed to mitotic interference and potential nucleic acid-directed alterations of hydrogen bond-based interactions impairing nucleic acid replication and transcription, a finding consistent with earlier reports [10,28,32,40,45,46]. This evidence concerns the gene CDKN1A and melanoma.