ORGAN-SPECIFIC OXIDATIVE DNA-DAMAGE ASSOCIATED WITH NORMAL BIRTH IN RATS (VOL 17, PG 2563, 1996)

Mammalian DNA contains bulky endogenous DNA modifications (I-compounds ), which increase with age in unexposed animals, as shown by P-32-post labeling. We have examined the perinatal formation of a subclass (type II) of I-compounds in rat liver, kidney, skin and lung, These I-compo unds represent bulky oxidative DNA lesions, defined herein as intrastr and base-base and base-sugar cross-links, adducts of lipid peroxidatio n products and DNA-protein cross-links, We observed a rapid increase i n the levels of five bulky oxidative DNA lesions during the first hour s 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 bir th in blood and tissues, implying inadequate antioxidant defenses in t he affected neonatal organs, Hepatic oxidative damage appeared intensi fied by increased concentrations of pro-oxidants and reduced concentra tions 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 wo uld 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 hith erto unrecognized role in spontaneous carcinogenesis and age-related d egenerative diseases.