Active oxygen generated in the process of carcinogen metabolism can induce oxidative damage in nuclei.
In the present study, we examined whether active oxygen formed in the process of 4-nitroquinoline 1-oxide (4NQO) reduction by DT-diaphorase could induce oxidative stress on the pulmonary nuclei. The rapid production of OH- radical-like species after the start of the 4NQO reduction was observed, and subsequent induction of nuclear lipid peroxidation occurred. In conjugation with this event, DNA damage estimated as DNA single strand breaks (DNA-SSB) increased in a time-dependent manner. The induction of this DNA damage was partially inhibited by mannitol or vitamin E treatment. These findings suggest that the active oxygen generated in the process of the 4NQO reduction can induce oxidative damage on the pulmonary nuclei.
Yano
T
T
Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, Japan.
Takahashi
S
S
Ichikawa
T
T
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects* / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*
D004277:DNA, Single-Stranded; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D015112:4-Nitroquinoline-1-oxide; D016660:NAD(P)H Dehydrogenase (Quinone)