Contribution of oxygen radicals to DNA cleavage by quinone compounds derived from phenolic antioxidants, tert-butylhydroquinone and 2,5-di-tert-butylhydroquinone.
The effects of synthetic phenolic antioxidants, tert-butylhydroquinone (TBHQ), 2,5-di-tert-butylhydroquinone (DTBHQ) and 3-tert-butyl-4-hydroxyanisole (BHA), on DNA cleavage were examined with supercoiled plasmid DNA, pUC18, in vitro. Extensive single and double strand breaks of DNA by TBHQ were observed and almost all the DNA was converted to the linear form at 10(-2) M. The cleavage was stimulated by both CuCl2 and FeCl2, though the effect of FeCl2 was smaller. Metal ion chelators and some oxygen radical scavengers inhibited the cleavage. The generation of TBHQ semiquinone radical and hydroxyl radical in the presence of copper was demonstrated by ESR spectroscopy. DTBHQ also caused DNA cleavage, though its effect was much smaller than that of TBHQ. BHA had no effect in the experimental systems employed. Oxygen radicals were considered to contribute to the DNA cleavage by TBHQ and DTBHQ.
Okubo
T
T
Department of Toxicology, The Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Nagai
F
F
Ushiyama
K
K
Kano
I
I
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000378:metabolism; D003300:Copper / Q000494:pharmacology; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects*; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D006873:Hydroquinones / Q000378:metabolism*; D008647:Mesocricetus; D011809:Quinones / Q000138:chemical synthesis / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D005296:Ferrous Compounds; D005609:Free Radicals; D006873:Hydroquinones; D011809:Quinones; D017382:Reactive Oxygen Species; D002083:Butylated Hydroxyanisole; C019359:2,5-di-tert-butylhydroquinone; D003300:Copper; C018855:2-tert-butylhydroquinone; C029892:cupric chloride; C029451:ferrous chloride