Glutathionyl hydroquinone: a potent pro-oxidant and a possible toxic metabolite of benzene.
Iron catalysed bleomycin (an antitumor antibiotic)-dependent degradation of DNA was investigated in the presence of glutathionyl hydroquinone (GHQ). DNA degradation was enhanced twelve-fold in the presence of iron and GHQ and three-fold in the presence of iron and glutathione (GSH) as compared to iron alone. The degradation of DNA was linear with the increase in concentration of GHQ or GSH keeping the iron, bleomycin and other factors constant. The presence of oxyradical scavengers, viz., thiourea, mannitol, albumin, superoxide dismutase, catalase and dimethyl sulfoxide caused significant inhibition of degradation of DNA by GHQ and iron. All the externally added GHQ to bone marrow cell lysate was completely demonstrable by the assay of iron-catalyzed bleomycin-dependent degradation of DNA. Superoxide radical generation was demonstrable during the incubation of GHQ. Thus, the present study revealed that GHQ is a potent pro-oxidant and this observation is significant in understanding the mechanism of benzene toxicity with the possibility of GHQ as one of the toxic metabolites of benzene.
Rao
G S
GS
Industrial Toxicology Research Centre, Lucknow, India.
D000818:Animals; D001554:Benzene / Q000378:metabolism* / Q000633:toxicity*; D016227:Benzoquinones / Q000737:chemistry; D001761:Bleomycin / Q000494:pharmacology; D001853:Bone Marrow / Q000737:chemistry; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D005296:Ferrous Compounds / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017382:Reactive Oxygen Species / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016227:Benzoquinones; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D001761:Bleomycin; D013481:Superoxides; C020748:ferrous sulfate; C004532:quinone; C040166:2-(S-glutathionyl)hydroquinone; D004247:DNA; D005978:Glutathione; D001554:Benzene