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.
Wataya
Y
Y
Faculty of Pharmaceutical Sciences, Okayama University.
Yamane
K
K
Hiramoto
K
K
Ohtsuka
Y
Y
Okubata
Y
Y
Negishi
K
K
Hayatsu
H
H
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002460:Cell Line; D004277:DNA, Single-Stranded / Q000187:drug effects; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014343:Trypan Blue
D002243:Carbolines; D004277:DNA, Single-Stranded; D013481:Superoxides; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D014343:Trypan Blue; D010100:Oxygen