Abstract
The antimalarial sulfone, dapsone, produces hemolysis and agranulocytosis. A metabolite of dapsone, 4-amino-4′-hydroxylaminodiphenyl sulfone (DDS-NOH) generates superoxide anion and hydrogen peroxide in vitro. To study a potential oxidant mechanism for agranulocytosis, we examined the effect of DDS-NOH on altering stem cell proliferation in vitro. Human bone marrow cells (2 × 105 cells/culture plate) were exposed to DDS-NOH for one hour at 37°C, washed, and then cultured in semi-soft agar for 14 days. The majority of colonies were granulocytic and their number (mean ± SD) were: Trypan blue exclusion by nucleated marrow cells was impaired at 1mM DDS-NOH. With 0.1mM DDS-NOH, addition of superoxide dismutase (SOD) or lactoperoxidase, sodium iodide, and SOD further decreased colony numbers, while catalase partially restored colony formation. These studies demonstrate that dapsone induced agranulocytosis may be mediated by oxidant damage to bone marrow stem cells and suggests that SOD may enhance sulfone induced oxidant injury.
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