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 32P-postlabeling, their levels are enhanced by pro-oxidant genotoxins and also shortly after normal birth in several rat tissues as a function of time and the maternal diet. In order to elucidate which dietary components contribute to postnatal DNA damage, we have focused, herein, on the possible role of transition metals (iron, copper, and nickel). Pregnant Fischer 344 (F344) rats were fed AIN-93G purified diet containing different amounts of iron, copper, and nickel, or Purina-5001 natural-ingredient diet (which contains relatively high concentrations of these metals). Type II I-compounds were estimated by nuclease P1-enhanced 32P-postlabeling in liver and lung DNA of fetuses and at 24h and day 9 post-partum. Increased postnatal oxidative damage was detected in liver but not lung DNA of neonates exposed to higher amounts of dietary transition metals. There were significant positive linear correlations between maternal transition metal intake and neonatal, but not fetal and maternal type II I-compound levels. The results show that transition metals in the maternal diet affect perinatal oxidative DNA damage, presumably via a Fenton-type reaction. They also provide evidence for optimal levels in the maternal diet of transition metals, which on one hand, are essential for life, but on the other, can cause potentially deleterious DNA alterations in the offspring.
Zhou
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GD
Division of Toxicology, Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Randerath
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E
Randerath
K
K
D000818:Animals; D000831:Animals, Newborn; D002855:Chromatography, Thin Layer; D003300:Copper / Q000494:pharmacology; D004249:DNA Damage; D005260:Female; D007501:Iron / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000196:embryology; D008168:Lung / Q000187:drug effects / Q000196:embryology; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008670:Metals / Q000737:chemistry*; D009154:Mutation; D009532:Nickel / Q000494:pharmacology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D049590:Postpartum Period; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D008670:Metals; D003300:Copper; D009532:Nickel; D007501:Iron; D010100:Oxygen