The effect of oxidative stress on nucleotide-excision repair in colon tissue of newborn piglets |
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Authors: | Sabine AS Langie Pawel Kowalczyk Barbara Tudek Romuald Zabielski Tomasz Dziaman Ryszard Oliński Frederik J van Schooten Roger WL Godschalk |
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Institution: | 1. Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands;2. Institute of Biochemistry and Biophysics PAS, Warsaw, Poland;3. Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Poland;4. Institute of Genetics and Biotechnology, Warsaw University, Poland;5. Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland;6. Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland |
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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 (200 mg) 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. |
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