INDUCTION OF 8-HYDROXY-2'-DEOXYGUANOSINE IN CHO-K1 CELLS EXPOSED TO PHENYL-HYDROQUINONE, A METABOLITE OF ORTHO-PHENYLPHENOL

The induction of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an index of oxi dative DNA modification, was investigated in CHO-K1 cells exposed to p henyl-hydroquinone (PHQ), a major metabolite of ortho-phenylphenol (OP P), an antimicrobial. Addition of PHQ at a concentration of 50 mu M to CHO cell suspensions (10(6) cells/ml) induced slight elevation of int racellular 8-OHdG levels. Pretreatment of CHO cells with 3-amino-1,2,4 -triazole (AT, 20 mM) enhanced PHQ-induced 8-OHdG formation which was accompanied by cell death. Pretreatment of CHO-K1 cells with AT (20 mM ) and deferoxamine (DeFe, 20 mM) inhibited the formation of 8-OHdG as well as cell death caused by PHQ. Neither AT nor DeFe affected cell vi ability or the formation of 8-OHdG in untreated CHO cells during the i ncubation period. The loss of cellular glutathione induced by the addi tion of PHQ alone was enhanced by the pretreatment of CHO cells with A T or AT plus DeFe. When PHQ was added to AT-pretreated cell suspension s, the concentration of PHQ decreased with time. This decease was acco mpanied by the formation of phenyl-benzoquinone (PBQ). These results s uggest that the reactive oxygen species derived from autoxidation of P HQ which converts to PBQ via phenyl-semiquinone elicit DNA damage in C HO cells, especially when the activity of cellular catalase is inhibit ed.