The in Vitro Action of Dapsone and its Derivatives on Normal and G6PD‐deficient Red Cells

Summary. In an attempt to define the mechanism of dapsone‐induced haemolysis the in vitro action of dapsone (4,4′, diaminodiphenylsulphone) and some of its derivatives on normal and G6PD‐deficient red cells has been investigated. Dapsone, its N′ acetyl‐ and hydroxy‐derivatives have no measurable effect on metabolism, haemoglobin or the membrane in either normal or G6PD‐deficient red cells. 4, hydroxylamino‐4′ aminodiphenylsulphone (HADS) and 4, hydroxylamino‐4′ acetaminodiphenylsulphone (HMDS) have oxidant effects on red cells. Both of these compounds readily form methaemoglobin but in normal red cells higher levels of methaemoglobin are achieved with HMDS than with HADS. With both compounds less methaemoglobin is formed in glucose‐deprived or in G6PD‐deficient red cells. In normal red cells hexose monophosphate pathway (HMP) activity is increased, HADS being a more potent stimulus than HMDS. It is suggested that methaemoglobin formation is dependent upon the recycling of these compounds via the HMP. Normal red cells incubated with the two hydroxylamine compounds did not show any change in reduced glutathione (GSH), globin or the membrane, apart from increased sensitivity to peroxide lysis. G6PD‐deficient red cells, on the other hand, did lose GSH rapidly and underwent increased autohaemolysis. The mechanism of these effects is discussed. Some, but not all, of the in vivo effects of dapsone can be reproduced by the hydroxylamine derivatives in vitro. It is concluded that either some other derivatives are involved or that the effect of long exposure to these oxidant compounds in vivo is different.