Carcinogenesis, Vol 18, 859-866, Copyright © 1997 by Oxford University Press
E Randerath, GD Zhou and K Randerath
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.
ARTICLES
Organ-specific oxidative DNA damage associated with normal birth in rats [corrected and republished article originally printed in Carcinogenesis 1996 Dec;17(12):2563-70]
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
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