title: Organ-specific oxidative DNA damage associated with normal birth in rats.
abstract: Mammalian DNA contains bulky endogenous DNA modifications (I-compounds), which increase with age in unexposed animals, as shown by 32P-postlabeling. We have examined the perinatal formation of a subclass (type II) of I-compounds in rat liver, kidney, skin and lung. These I-compounds represent bulky oxidative DNA lesions, defined herein as intrastrand base-base and base-sugar cross-links, adducts of lipid peroxidation products and DNA-protein cross-links. We observed a rapid increase in the levels of five bulky oxidative DNA lesions during the first hours after normal birth of rats, with total levels increasing 4.2-, 3.0- and 1.3-fold, respectively, in liver, kidney and skin. This effect was not noted in lung. The results were consistent with oxidative stress induced by the known sudden increase in partial oxygen pressure at birth in blood and tissues, implying inadequate antioxidant defenses in the affected neonatal organs. Hepatic oxidative damage appeared intensified by increased concentrations of pro-oxidants and reduced concentrations of antioxidants in the maternal diet. The postnatal DNA lesions are postulated to be premutagenic, as indicated by their bulky nature and persistence. Pathophysiological effects of oxidative DNA damage would be exacerbated by rapid cell proliferation in neonatal tissues and consequent fixation as mutations. In addition to inherited mutations, DNA lesions acquired as a consequence of normal birth may play a hitherto unrecognized role in spontaneous carcinogenesis and age-related degenerative diseases.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: E
authors.initials: E
authors.lastname: Randerath
authors.forename: G D
authors.initials: GD
authors.lastname: Zhou
authors.forename: K
authors.initials: K
authors.lastname: Randerath
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D018736:DNA Adducts; D004249:DNA Damage; D004032:Diet; D009928:Organ Specificity; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
chemical_list: D018736:DNA Adducts