Induction of the SOS DNA repair response in Escherichia coli by nitric oxide donating agents: dinitrosyl iron complexes with thiol-containing ligands and S-nitrosothiols.
The ability of nitric oxide (NO) donor compounds to induce the SOS DNA repair response in Escherichia coli is reported. Dinitrosyl iron complexes with glutathione and cysteine (DNIC) are the most potent SOS-inducers. S-Nitrosothiols (RSNO) mediate a similar response at 10-100 microM, but the response decreases sharply at concentrations above 0.5 mM. Pretreatment of the cells with the chelating agent o-phenanthroline (OP) prevents induction of the SOS response by all agents used. On the other hand, the toxicity of S-nitrosothiols is higher than that of DNIC. The EPR study shows the appearance of an EPR DNIC-type signal after incubation of the cells with S-nitrosoglutathione because of mutual transformation between RSNO and DNIC in the presence of accessible iron inside the cells. Pretreatment of the cells with OP leads to a decrease in this signal. Analysis of NO donor effects reveals a dual role of the iron ions in reactivity and toxicity of the compounds studied, i.e. (i) stabilization of the cytotoxic RSNO and (ii) generation of the SOS signal.
Lobysheva
I I
II
Institute of Chemical Physics, Russian Academy of Sciences, Moscow. irlobysh@polymer.chph.ras.ru
Stupakova
M V
MV
Mikoyan
V D
VD
Vasilieva
S V
SV
Vanin
A F
AF
D004260:DNA Repair / Q000187:drug effects*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008024:Ligands; D008623:Mercaptoethanol; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000378:metabolism; D026403:S-Nitrosothiols
D004269:DNA, Bacterial; D008024:Ligands; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D007501:Iron