Acta Biochimica Polonica 51(4), 1081-1086
Enzymatic redox reactions of the explosive 4,6-dinitrobenzofuroxan (DNBF): implications for its toxic action.
Aušra Nemeikaite-Ceniene1, Jonas Sarlauskas2, Lina Miseviciene2, Zilvinas Anusevicius2, Audrone Maroziene2 and Narimantas Cenas2, e-mail
1Institute of Immunology, Moletu Pl. 29, Vilnius 2021, Lithuania; 2Institute of Biochemistry, Mokslininku 12, Vilnius 2600, Lithuania
Key words: nitroaromatic explosives, cytotoxicity, oxidative stress
With an aim to understand the toxicity mechanisms of the explosive 4,6-dinitro- benzofuroxan (DNBF), we studied its single-electron reduction by NADPH:cytochrome P450 reductase and ferredoxin:NADP+ reductase, and two- electron reduction by DT-diaphorase and Enterobacter cloacae nitroreductase. The enzymatic reactivities of DNBF and another explosive 2,4,6-trinitrotoluene (TNT) were similar, except for the much lower reactivity of DNBF towards nitroreductase. DNBF was less cytotoxic in FLK cells than TNT. However, their action shared the same mechanisms, oxidative stress and activation by DT-diaphorase. The lower cytotoxicity of DNBF may be explained by the negative electrostatic charge of its adduct with water which may impede cellular membrane penetration, and by the formation of its less reactive adducts with intracellular reduced glutathione.