Document 0798
 DOCN  M94B0798
 TI    Replication inhibition and miscoding properties of a DNA template
       containing N-(deoxyguanosin-8-yl)-1-aminopyrene (Meeting abstract).
 DT    9412
 AU    Vyas RR; Basu AK; Dept. of Chemistry, Univ. of Connecticut, Storrs, CT
       06269
 SO    Proc Annu Meet Am Assoc Cancer Res; 35:A854 1994. Unique Identifier :
       AIDSLINE ICDB/94602541
 AB    A major DNA adduct formed by the environmental pollutant 1-nitropyrene
       is N-(deoxyguanosin-8-yl)-1-aminopyrene (dG(AP)). We have synthesized a
       DNA fragment that contained this adduct at a specific site. A primer was
       annealed to this template and in vitro DNA synthesis by a variety of
       polymerases was studied. Primer extension catalyzed by HIV reverse
       transcriptase, a modified T7 DNA polymerase (Sequenase), human DNA
       polymerase alpha, or DNA polymerase beta was inhibited almost
       quantitatively at the base 3' to the adduct site even when high
       concentration of the polymerase and/or dNTPs were employed. When
       3'----5' exonuclease-free Klenow fragment of the DNA polymerase I was
       used, efficient nucleotide incorporation opposite the adduct was
       observed. However, dGTP and dATP were preferentially incorporated
       opposite dG(AP). In the presence of Mg2+, extension beyond the adduct
       site did not occur. In the presence of Mn2+, on the other hand,
       significant proportion of the primer was extended to a full-length
       product. This suggests that dG(AP) can induce both genotoxic and
       mutagenic effects in vivo.
 DE    Comparative Study  DNA Polymerase I/METABOLISM  DNA Polymerase
       II/METABOLISM  DNA Polymerases/*METABOLISM  DNA Primers  *DNA
       Replication/DRUG EFFECTS  Deoxyguanosine/*ANALOGS &
       DERIVATIVES/METABOLISM  Environmental Pollutants/*TOXICITY
       Exodeoxyribonucleases/METABOLISM  HIV/ENZYMOLOGY  Human
       Pyrenes/*ANALYSIS/METABOLISM/*TOXICITY  Reverse
       Transcriptase/*METABOLISM  Templates  MEETING ABSTRACT

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