Generation of intracellular active oxygens in mouse FM3A cells by 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole, the activated Trp-P-2.

Mouse FM3A cells in culture were treated with a reactive metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2-(NHOH]. When the treated cells, which were judged as viable on the basis of trypan-blue exclusion, were subjected to nitroblue tetrazolium staining, formazan was formed inside the cells, a fact suggesting the intracellular presence of superoxide. No formazan formation was detected on treatment of the cells with Trp-P-2. Single-strand breaks in the cellular DNA took place during this treatment with Trp-P-2(NHOH). Since Trp-P-2(NHOH) in solution generates superoxide anion accompanying its oxidative degradation, we conclude that the Trp-P-2(NHOH) treatment produces intracellular active oxygens that can damage DNA.