Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative damage to cellular DNA

Phenolic phytoehemicals are natural plant substances whose cellular effects have not been completely determined. Nordihydroguaiaretic acid (NDGA) and curcumin are two phenolic phytochemicals with similar molecular structures, suggesting that they possess comparable chemical properties particularly i n terms of antioxidant activity. To examine this possibility in a cellular system, this study evaluated the capacities of NDGA and curcumin to functio n as antioxidants in inhibiting oxidative damage to DNA. Jurkat T-lymphocyt es were pre-incubated for 30 min with 0-25 muM of either NBGA or curcumin t o allow for uptake. The phenolic phytochemical-treated cells were then oxid atively challenged with 25 muM hydrogen peroxide (H2O2). Afterwards, cells were subjected to alkaline micro-gel electrophoresis (i.e. comet assay) to assess the extent of single-strand breaks in DNA. In a concentration-depend ent manner, NDGA inhibited H2O2-induced DNA damage, whereas curcumin did no t. In fact, incubating Jurkat T-lymphocytes with curcumin alone actually in duced DNA damage. This effect of curcumin on DNA did not appear to reflect the DNA fragmentation associated with apoptosis because there was no proteo lytic cleavage of poly-(ADP-ribose)-polymerase, which is considered an earl y marker of apoptosis. Curcumin-induced damage to DNA was prevented by pre- treatment of the cells with the lipophilic anti oxidant, alpha -tocopherol, suggesting that curcumin damaged DNA through oxygen radicals. Therefore, i t is concluded that NDGA has antioxidant activity but curcumin has prooxida nt activity in cultured cells based on their opposite effects on DNA. (C) 2 001 Elsevier Science B.V. All rights reserved.