PMID- 8569792
OWN - NLM
STAT- MEDLINE
DCOM- 19960305
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 349
IP  - 1
DP  - 1996 Jan 17
TI  - Peroxynitrite-induced mutation spectra of pSP189 following replication in 
      bacteria and in human cells.
PG  - 51-61
AB  - Peroxynitrite is a powerful oxidant formed through reaction of nitric oxide with 
      superoxide. Because activated macrophages can produce both nitric oxide and 
      superoxide, it has been proposed that peroxynitrite may contribute to 
      cytotoxicity and increased cancer risks associated with the inflammatory response 
      during chronic infections. We therefore investigated mutagenicity of 
      peroxynitrite in the supF gene of the pSP189 shuttle vector as a mutation target. 
      The plasmid was exposed to 2.5 mM peroxynitrite in vitro, then replicated in 
      Eschericia coli MBL50 and in human AD293 cells. Mutation frequency increased 
      21-fold in pSP189 replicated in E. coli and 9-fold in plasmid replicated in human 
      cells. Mutations were clustered within the 5' region of the supF gene in plasmids 
      replicated in bacteria. The hot spots were located at positions 108, 113, 116, 
      124, 126 and 141; more than 25% of all mutations occurred at position 124. 
      Following replication in human cells, mutations were more widely distributed over 
      the gene, with hot spots at positions 113, 124, 133, 156 and 164; 15% occurred at 
      position 124. In both systems, the majority of mutations occurred at G:C base 
      pairs, predominantly involving G:C-->T:A transversions (65% when replication was 
      in bacteria and 63% when in human cells). G:C-->C:G transversions were observed 
      at lower frequency (28% in MBL50 and 11% in AD293 cells), and 11% of mutations 
      found in vectors replicated in AD293 cells were G:C-->A:T transitions. A greater 
      number of large deletions, insertions, tandem and multiple mutations occurred in 
      plasmid replicated in AD293 cells. Differences in mutation spectra following 
      replication in the two systems may be attributable to differences in recognition 
      and repair of the lesions and/or properties of the replication apparatus.
FAU - Juedes, M J
AU  - Juedes MJ
AD  - Massachusetts Institute of Technology, Division of Toxicology, Cambridge 02139, 
      USA.
FAU - Wogan, G N
AU  - Wogan GN
LA  - eng
GR  - 2P01CA26731/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (DNA, Recombinant)
RN  - 0 (Mutagens)
RN  - 0 (Nitrates)
RN  - 0 (Oxidants)
RN  - 0 (supF tRNA)
RN  - 26404-66-0 (peroxynitric acid)
RN  - 9014-25-9 (RNA, Transfer)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Replication
MH  - DNA, Recombinant
MH  - Escherichia coli/genetics
MH  - Genes, Suppressor/*drug effects
MH  - Genetic Vectors/*drug effects/genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenicity Tests
MH  - Mutagens/*toxicity
MH  - Nitrates/*toxicity
MH  - Oxidants/*toxicity
MH  - RNA, Transfer/*genetics
EDAT- 1996/01/17 00:00
MHDA- 1996/01/17 00:01
CRDT- 1996/01/17 00:00
PHST- 1996/01/17 00:00 [pubmed]
PHST- 1996/01/17 00:01 [medline]
PHST- 1996/01/17 00:00 [entrez]
AID - 0027510795001522 [pii]
AID - 10.1016/0027-5107(95)00152-2 [doi]
PST - ppublish
SO  - Mutat Res. 1996 Jan 17;349(1):51-61. doi: 10.1016/0027-5107(95)00152-2.