title: The effect of oxidative stress on nucleotide-excision repair in colon tissue of newborn piglets.
abstract: Nucleotide-excision repair (NER) is important for the maintenance of genomic integrity and to prevent the onset of carcinogenesis. Oxidative stress was previously found to inhibit NER in vitro, and dietary antioxidants could thus protect DNA not only by reducing levels of oxidative DNA damage, but also by protecting NER against oxidative stress-induced inhibition. To obtain further insight in the relation between oxidative stress and NER activity in vivo, oxidative stress was induced in newborn piglets by means of intra-muscular injection of iron (200mg) at day 3 after birth. Indeed, injection of iron significantly increased several markers of oxidative stress, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels in colon DNA and urinary excretion of 8-oxo-7,8-dihydroguanine (8-oxoGua). In parallel, the influence of maternal supplementation with an antioxidant-enriched diet was investigated in their offspring. Supplementation resulted in reduced iron concentrations in the colon (P=0.004) at day 7 and a 40% reduction of 8-oxodG in colon DNA (P=0.044) at day 14 after birth. NER capacity in animals that did not receive antioxidants was significantly reduced to 32% at day 7 compared with the initial NER capacity on day 1 after birth. This reduction in NER capacity was less pronounced in antioxidant-supplemented piglets (69%). Overall, these data indicate that NER can be reduced by oxidative stress in vivo, which can be compensated for by antioxidant supplementation.
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands.
authors.forename: Sabine A S
authors.initials: SA
authors.lastname: Langie
authors.forename: Pawel
authors.initials: P
authors.lastname: Kowalczyk
authors.forename: Barbara
authors.initials: B
authors.lastname: Tudek
authors.forename: Romuald
authors.initials: R
authors.lastname: Zabielski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dziaman
authors.forename: Ryszard
authors.initials: R
authors.lastname: Oliński
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004032:Diet; D007273:Injections, Intramuscular; D007501:Iron / Q000494:pharmacology; D007505:Iron-Dextran Complex / Q000008:administration & dosage; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013054:Spectrophotometry, Atomic; D013552:Swine
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007505:Iron-Dextran Complex; D007501:Iron; D003849:Deoxyguanosine