Pro-oxidative interactions of dithranol with human phagocytes promote oxidative damage to DNA of bystander leucocytes.
Dithranol at therapeutic concentrations (5-40 micrograms ml-1) induced strand breaks in human leucocyte DNA in vitro in a dose-related manner. Leucocytes from individuals with chronic granulomatous disease (CGD) incurred substantially less DNA strand breaks than did normal leucocytes during exposure to dithranol indicating that activated phagocytes are involved. H-7, 4-beta-bromophenacyl bromide (BPB) and staurosporine, all inhibitors of protein kinase C, decreased both dithranol-mediated activation of the phagocyte respiratory burst and induction of DNA strand breaks. Similar effects were observed with the hydrogen peroxide scavenger catalase. These results suggest that dithranol induces DNA strand breaks, mainly as a result of pro-oxidative interactions with phagocytes.
Forrester
D M
DM
Department of Immunology, University of Pretoria, Republic of South Africa.
Van Rensburg
C E
CE
Anderson
R
R
D000098:Acetophenones / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000875:Anthralin / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage; D006105:Granulomatous Disease, Chronic / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008163:Luminescent Measurements; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010586:Phagocytes / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine
D000098:Acetophenones; D000470:Alkaloids; D002374:Catalase; D011493:Protein Kinase C; D019311:Staurosporine; C006821:4-bromophenacyl bromide; D000875:Anthralin