Effects of dietary transition metals on oxidative DNA lesions in neonatal rats

Bulky endogenous oxidative lesions (type II I-compounds) reflect DNA damage associated with oxidative stress. As shown by P-32-postlabeling, their lev els are enhanced by pro-oxidant genotoxins and also shortly after normal bi rth in several rat tissues as a function of dme and the maternal diet. In o rder to elucidate which dietary components contribute to postnatal DNA dama ge, we have focused, herein, on the possible role of transition metals (iro n, copper, and nickel). Pregnant Fischer 344 (F344) rats were fed AIN-93G p urified diet containing different amounts of iron, copper, and nickel, or P urina-5001 natural-ingredient diet (which contains relatively high concentr ations of these metals). Type III-compounds were estimated by nuclease PI-e nhanced P-32-postlabeling in liver and lung DNA of fetuses and at 24h and d ay 9 post-partum. Increased postnatal oxidative damage was detected in live r but not lung DNA of neonates exposed to higher amounts of dietary transit ion metals. There were significant positive linear correlations between mat ernal transition metal intake and neonatal, but not fetal and maternal type II I-compound levels. The results show that transition metals in the mater nal diet affect perinatal oxidative DNA damage, presumably via a Fenton-typ e reaction. They also provide evidence for optimal levels in the maternal d iet of transition metals, which on one hand, are essential for life, but on the other, can cause potentially deleterious DNA alterations in the offspr ing. (C) 2001 Elsevier Science B.V. All rights reserved.