FORMATION OF 8-HYDROXYDEOXYGUANOSINE IN CALF THYMUS DNA TREATED WITH TERT-BUTYLHYDROQUINONE, A MAJOR METABOLITE OF BUTYLATED HYDROXYANISOLE

Oxidative DNA damage caused by butylated hydroxyanisole (BHA), 2-tert- butyl(1,4)hydroquinone (TBHQ, a metabolite of BHA) and 2,5-di-tert-but yl(1,4)hydroquinone (DTBHQ), as well as 2,6-di-tert-butyl(1,4)benzoqui none (BHTQ, a metabolite of butylated hydroxytoluene), was evaluated b y measuring the formation of 8-hydroxy-deoxyguanosine (8OHdG) in calf thymus DNA. 8OHdG formation was greatly increased by TBHQ in a concent ration-dependent manner. This effect was strongly enhanced by CuCl2 an d suppressed by EDTA, bathocuproinedisulfonic acid disodium salt, meth ionine, glutathione reduced form or catalase, but was not affected by mannitol, sodium benzoate or sodium azide. Thus, TBHQ-induced 8OHdG fo rmation may be mediated by copper. DTBHQ also induced the formation of 8OHdG, though to a much lesser extent than TBHQ, and its effect was s timulated by CuCl2. BHA had a small enhancing effect at high concentra tion, only in the presence of CuCl2, whereas in the case of BHTQ, it o ccurred both in the presence of CuCl2 and FeCl2.