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-hydr oxyanisole (BHA), on DNA cleavage were examined with supercoiled plasm id 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 an d some oxygen radical scavengers inhibited the cleavage. The generatio n of TBHQ semiquinone radical and hydroxyl radical in the presence of copper was demonstrated by ESR spectroscopy. DTBHQ also caused DNA cle avage, though its effect was much smaller than that of TBHQ. BHA had n o effect in the experimental systems employed. Oxygen radicals were co nsidered to contribute to the DNA cleavage by TBHQ and DTBHQ. Copyrigh t (C) 1997 Elsevier Science Ireland Ltd.