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I hope this helps. Oxidative DNA damage as a marker of arsenic trioxide-induced toxicity in human promyelocytic leukaemia HL-60 cells. Arsenic trioxide (As(2)O(3)) has been shown to be an effective treatment for patients with acute promyelocytic leukaemia (APL). However, its clinical use is restricted by a narrow therapeutic index. Therefore, a detailed understanding of the mechanisms by which As(2)O(3) causes toxicity in APL cells is of prime importance. In this study, the relationship between the mode of As(2)O(3) toxicity and apoptosis was studied. In HL-60 cells, As(2)O(3) induced a decrease in the activity of the topoisomerase II enzyme, an increase in the amount of DNA breaks, and the formation of 8-oxoguanine, indicating that As(2)O(3) is a potent mutagen. In parallel, DNA fragmentation in the nuclei of the cells and the cleavage of poly (ADP-ribose) polymerase, an indicator of DNA damage, were also observed. The ability of As(2)O(3) to induce apoptosis, which is strongly related to the mode of its toxicity, was examined by three different approaches. As(2)O(3) induced the accumulation of cells in the G(2)/M phase of the cell cycle, along with a concomitant decrease in the G(1) phase. Furthermore, the formation of DNA strand breaks, and the induction of apoptosis in these cells, were highly correlated with the decrease in the expression of the cell cycle regulators Cdc25A, cyclin B, and p21(WAF1/CIP1). These results indicate that As(2)O(3) induces the accumulation of DNA damage, leading to apoptosis in HL-60 cells.Australia has a “defensive” climate denial movement and a trend toward “green tyranny”, according to a report released on Tuesday by a leading climate sceptic group. The climate sceptic, British-based Global Warming Policy Foundation (GWPF) is a nonprofit organisation with a mission to promote “skeptical scrutiny” of global warming claims. In its report, prepared in response to demands from the Australian government for an independent assessment of climate change policy, the foundation



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