INCREASED 8-HYDROXYDEOXYGUANOSINE IN KIDNEY AND LIVER OF RATS CONTINUOUSLY EXPOSED TO COPPER

Copper is a ubiquitous metal in the environment, it is a component of dental casting gold alloys and dental amalgams, and it is a main compo nent in some intrauterine contraceptive devices (IUDs). Since copper m aterials implanted in the human body corrode and release ions into the surrounding tissue, the potential toxicity caused by contact of this metal with bodily fluids needs to be evaluated. We implanted male Wist ar rats with osmotic mini pumps that continuously administered saline, CuCl2, or a copper chelate, cupric nitrilotriacetate (Cu-NTA), at a r ate of 4 mg copper/kg body wt/day. This experimental design maintained serum copper concentrations at a level 30-70% (CuCl2) or 100-120% (Cu -NTA) higher than in untreated controls. At different times postimplan tation, we measured the levels of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of kidney, liver, and tissue surrounding the pump implant, since p roduction of 8-OHdG has been associated with mutagenesis and carcinoge nesis. Hepatic and renal levels of 8-OHdG in CuCl2- or Cu-NTA-treated animals were significantly higher than in control animals. In contrast , histopathologic changes in kidneys and livers of rats exposed to CuC l2 and Cu-NTA were limited to mild changes involving hepatic focal nec rosis and slightly increased mitotic activity in the renal proximal tu bules. These observations suggest that levels of 8-OHdG could be an ea rly marker of copper toxicity. It is unlikely that the high levels of copper at which we observed DNA modification will be encountered after occupational or environmental exposure. A different situation could b e found around medical devices that include copper, particularly IUDs, where the amount of copper administered in our experiments could be r eleased in the uterus of women after a few months of continued IUD use . (C) 1994 Academic Press, Inc.