In the present report we summarize the results of our recent work on the molecular mechanisms mediating DNA single strand breakage in U937 cells exposed to tert-butylhydroperoxide (tB-OOH) and describe the effects of exogenous nitric oxide (NO) on these responses. Low levels of NO donors, which likely release physiological concentrations of NO, enhance the accumulation of DNA single strand breaks in cells exposed to tB-OOH. This NO-mediated effect appears to be linked to inhibition of the electron transport from cytochrome b to cytochrome c1. Under these conditions, electrons are directly transferred from ubisemiquinone to molecular oxygen with concomitant formation of superoxides and H2O2. H2O2 then migrates to the nucleus and generates the DNA-damaging hydroxyl radicals via interaction with chromatin-bound divalent iron.
Effects of nitric oxide on tert-butylhydroperoxide-induced DNA single-strand breakage.
CANTONI, ORAZIO;GUIDARELLI, ANDREA;PALOMBA, LETIZIA;SESTILI, PIERO
2000
Abstract
In the present report we summarize the results of our recent work on the molecular mechanisms mediating DNA single strand breakage in U937 cells exposed to tert-butylhydroperoxide (tB-OOH) and describe the effects of exogenous nitric oxide (NO) on these responses. Low levels of NO donors, which likely release physiological concentrations of NO, enhance the accumulation of DNA single strand breaks in cells exposed to tB-OOH. This NO-mediated effect appears to be linked to inhibition of the electron transport from cytochrome b to cytochrome c1. Under these conditions, electrons are directly transferred from ubisemiquinone to molecular oxygen with concomitant formation of superoxides and H2O2. H2O2 then migrates to the nucleus and generates the DNA-damaging hydroxyl radicals via interaction with chromatin-bound divalent iron.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
