The toxicity of aromatic nitrocompounds to bovine leukemia virus-transformed fibroblasts: the role of single-electron reduction.
Bovine leukemia virus-transformed lamb embryo fibroblasts (line FLK) possess activity of DT-diaphorase of ca. 260 U/mg protein and similar levels of other NADP(H)-oxidizing enzymes: NADH:oxidase, 359 U/mg; NADPH:oxidase, 43 U/mg; NADH:cytochrome-c reductase, 141 U/mg; NADPH:cytochrome-c reductase, 43 U/mg. In general, the toxicity of aromatic nitrocompounds towards FLK cells increases on increase of single-electron reduction potentials (E1(1)) of nitrocompounds or the log of their reduction rate constants by single-electron-transferring enzymes, microsomal NADPH:cytochrome P-450 reductase (EC 1.6.2.4) and mitochondrial NADH:ubiquinone reductase (EC 1.6.99.3). No correlation between the toxicity and reduction rate of nitrocompounds by rat liver DT-diaphorase (EC 1.6.99.2) was observed. The toxicity is not significantly affected by dicumarol, an inhibitor of DT-diaphorase. Nitrocompounds examined were poor substrates for DT-diaphorase, being 10(4) times less active than menadione. Their poor reactivity is most probably determined by their preferential binding to a NADPH binding site, but not to menadione binding site of diaphorase. These data indicate that at comparable activities of DT-diaphorase and single-electron-transferring NAD(P)H dehydrogenases in the cell, the toxicity of nitrocompounds will be determined mainly by their single-electron reduction reactions.
Cènas
N
N
Institute of Biochemistry, Lithuanian Academy of Sciences, Mokslininku.
Nemeikaitè
A
A
Dickancaitè
E
E
Anusevicius
Z
Z
Nivinskas
H
H
Bironaitè
D
D
D000818:Animals; D002461:Cell Line, Transformed / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D001909:Leukemia Virus, Bovine; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D009252:NADPH Dehydrogenase / Q000037:antagonists & inhibitors*; D009574:Nitro Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011809:Quinones / Q000494:pharmacology; D012756:Sheep; D014812:Vitamin K / Q000037:antagonists & inhibitors
D009574:Nitro Compounds; D011809:Quinones; D014812:Vitamin K; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase