Document 0064
 DOCN  M9480064
 TI    Reverse chemical mutagenesis: identification of the mutagenic lesions
       resulting from reactive oxygen species-mediated damage to DNA.
 DT    9410
 AU    Feig DI; Sowers LC; Loeb LA; Department of Biochemistry, University of
       Washington, Seattle; 98195.
 SO    Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6609-13. Unique Identifier :
       AIDSLINE MED/94294428
 AB    An understanding of the contribution of reactive oxygen species to
       mutagenesis has been hampered by the vast number of different chemical
       modifications they cause in DNA. Even though many of these DNA
       alterations have been catalogued, the identification of specific lesions
       that cause mutations has depended on testing one modification at a time.
       In this study we present another approach to identify key mutagenic
       lesions from a pool of oxidatively modified nucleotides. dCTP was
       treated with an oxygen radical-generating system containing FeSO4, H2O2,
       and ascorbic acid. The modification products were separated by
       reverse-phase and anion-exchange HPLC and then incorporated by human
       immunodeficiency virus reverse transcriptase into a DNA that contains a
       target gene for scoring for mutations. One of the mutagenic species
       isolated was identified as 5-hydroxy-2'-deoxycytidine. It is
       incorporated efficiently into DNA and causes C-->T transitions in
       Escherichia coli at a frequency of 2.5%, which is more mutagenic than
       any previously identified oxidative DNA lesion.
 DE    Base Sequence  Deoxycytidine/ANALOGS & DERIVATIVES/ANALYSIS
       Deoxycytosine Nucleotides/*CHEMISTRY  Deoxyribonucleotides/METABOLISM
       *DNA Damage  DNA, Bacterial/DRUG EFFECTS/GENETICS/RADIATION EFFECTS
       DNA, Viral/BIOSYNTHESIS/RADIATION EFFECTS  Escherichia coli/DRUG
       EFFECTS/*GENETICS  Gamma Rays  Genes, Bacterial  HIV-1/*ENZYMOLOGY
       Molecular Sequence Data  *Mutagenesis  Mutagens/*TOXICITY
       Oxidation-Reduction  Phosphorus Radioisotopes  Reactive Oxygen Species
       Reverse Transcriptase/*METABOLISM  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).