Mode of Action for Mitomycin C Inactivating Factors of Pseudomonas convexa 4-87

Abstract

Mutagenicity of the anti-cancer agent mitomycin C was suppressed by incubation with the desmutagenic factor of Pseudomonas convexa 4-87 and NAD(P)H. The main reaction products were isolated and identified as 1,2-cis- and l,2-trans-2,7-diamino-l-hydroxymitosene and 2,7-diaminomitosene. A reaction scheme through reduction of the benzoquinone moiety, elimination of the methoxy group, opening of the aziridine ring, and formation of mitosene-type derivatives was proposed. The desmutagenic factor of P. convexa 4-87 was shown to be a quinone-reducing enzyme requiring NAD(P)H, but its physiological role in the cell remains unclear.