Enhanced levels in neonatal rat liver of 7,8-dihydro-8-oxo-2'- deoxyguanosine (8-hydroxydeoxyguanosine), a major mutagenic oxidative DNA lesion
Kurt Randerath
Abstract
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Kurt Randerath
Abstract
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The purpose of this study was to determine whether the level of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine) (8-oxo-dG), a major mutagenic DNA oxidation product, is enhanced in newborn rat liver DNA as a consequence of oxidative stress incurred during the early postnatal period. 32P-postlabeling showed this adduct to increase approximately 2-fold from the 20th day of gestation (2 days before birth) to a peak level at 50-53 h after birth. Postnatal levels exceeded fetal levels at all time points investigated, i.e. 0.5-1, 8, 24, 50-53, 100, 216 and 432 h after birth. Increased formation of this mutagenic DNA lesion during the critical postnatal phase when there is rapid cell proliferation in all tissues is proposed to contribute to carcinogenesis in susceptible tissues later in life.
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The purpose of this study was to determine whether the level of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine) (8-oxo-dG), a major mutagenic DNA oxidation product, is enhanced in newborn rat liver DNA as a consequence of oxidative stress incurred during the early postnatal period. 32P-postlabeling showed this adduct to increase approximately 2-fold from the 20th day of gestation (2 days before birth) to a peak level at 50-53 h after birth. Postnatal levels exceeded fetal levels at all time points investigated, i.e. 0.5-1, 8, 24, 50-53, 100, 216 and 432 h after birth. Increased formation of this mutagenic DNA lesion during the critical postnatal phase when there is rapid cell proliferation in all tissues is proposed to contribute to carcinogenesis in susceptible tissues later in life.
Key concepts: Deoxyguanosine, DNA oxidation, Carcinogenesis, Oxidative stress, Lesion, 8-Hydroxy-2'-deoxyguanosine, DNA, Fetus