Indigenous DNA adducts (I-compounds) are considered to be a biomarker of aging tissues. Thus far, few studies have been conducted to investigate the accumulation patterns of I-compounds in the brain during aging. Particularly, identities of age-dependent I-compounds have largely remained unknown. In the current study, we have determined the amounts of I-compounds in the brains of male Fischer 344 @entity35 at ages 1, 6, 12, 18, and 24 months using a 32P-postlabeling technique. The results indicate that I-compounds increase in the @entity35 brain age dependently from 6 to 24 months of age. Total I-adduct levels (central and upper cutouts) increase 3.5-fold from 6 to 24 months. Contrary to the results of other investigators, brains of 1-month-old @entity35 contain the highest level of I-compounds, which may be due to the @entity2495 status during the @entity1 period. In an effort to characterize I-compounds, different deoxynucleosides were coincubated with @entity1234 ( @entity1865 ). The results show that only @entity16614 ( @entity24849 )- @entity1865 adducts overlap with I-compounds of the @entity35 brain DNA adducts map. A total of five @entity24849 - @entity1865 adducts have been identified as responsible for I-compounds in brain tissues. It is known that brain tissue contains high levels of lipids that are susceptible to @entity26 free radicals and that @entity1865 is the most abundant and genotoxic product of lipid peroxidation. The present study provides supporting evidence that lipid peroxidation and its product ( @entity1865 ) may play an important role in endogenous brain DNA modification, which may partly contribute to cerebral aging and age-related @entity75 . The accumulation of I-compounds with aging may serve as an index of indirect oxidative damage to DNA as evidenced by the presence of @entity1865 -DNA adducts.

Age-dependent increase of indigenous DNA adducts in XXXX brain is associated with a lipid peroxidation product.

@entity1 :: ('9606', 'Species') :: ['infant'] @entity75 :: ('MESH:D001927', 'Disease') :: ['degenerative disorders of the brain'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity2495 :: ('MESH:C565498', 'Disease') :: ['hypermetabolic'] @entity1234 :: ('MESH:D008315', 'Chemical') :: ['malondialdehyde'] @entity16614 :: ('MESH:D003849', 'Chemical') :: ['deoxyguanosine'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity24849 :: ('MESH:C007257', 'Chemical') :: ['dGMP'] @entity1865 :: ('CHEBI:566274', 'Chemical') :: ['MDA']
@entity35 :: (10116,Species) :: ['rat']
