Effect of antioxidant phytochemicals on the hepatic tumor promoting activity of 3,3′,4,4′-tetrachlorobiphenyl (PCB-77)

Polychlorinated biphenyls (PCBs) have promoting activity in the liver, which may be brought about in part by the induction of oxidative stress. In this study we examined the effects of several antioxidant phytochemicals on the tumor promoting activity of 3,3',4'4-tetrachlorobiphenyl (PCB-77). Female Sprague Dawley rats were first injected with diethylnitrosamine (DEN, 150 mg/kg) and one week later the rats were fed an AIN-93 based purified diet or the same diet containing ellagic acid (0.4%), beta-carotene (0.5%), curcumin (0.5%), N-acetyl cysteine (NAC, 1.0%), coenzyme CoQ(10) (CoQ(10), 0.4%), resveratrol (0.005%), lycopene (10% as Lycovit, which contains 10% lycopene), or a tea extract (1%, containing 16.5% epigallocatechin-3-gallate [EGCG] and 33.4% total catechins). Rats were fed the diets for the remainder of the study. After three weeks, 2/3 of the control rats and all of the antioxidant diet-fed rats were injected i.p. with PCB-77 (300 mu mol/kg) every other week for four injections. All rats were euthanized ten days after the last PCB injection. The rats that received PCB-77 alone showed an increase in the number and size of placental glutathione S-transferase (PGST)-positive foci in the liver, Lycopene significantly decreased the number of foci, while curcumin and CoQ(10) decreased the size of the foci. In contrast, ellagic acid increased the number but decreased the size of the foci. All of the other phytochemicals showed only slight or no effects. Compared with the PCB-77 group, CoQ(10) increased cell proliferation in normal hepatocytes, whereas the other antioxidants had no effect in either normal or PGST-positive hepatocytes. These findings show that none of the antioxidant phytochemicals produced a clear decrease in the promoting activity of PCB-77. (C) 2008 Elsevier Ltd. All rights reserved.