PMID- 1988171
OWN - NLM
STAT- MEDLINE
DCOM- 19910225
LR  - 20190510
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 12
IP  - 1
DP  - 1991 Jan
TI  - Kinds of mutations found when a shuttle vector containing adducts of 
      1,6-dinitropyrene replicates in human cells.
PG  - 119-26
AB  - To gain insight into the mechanisms by which carcinogens induce mutations in 
      human cells, we have been comparing the frequency and spectrum of mutations 
      induced when a shuttle vector, pS189, carrying covalently bound residues of 
      structurally related carcinogens, replicates in human 293 cells. In the present 
      study, we investigated the mutagenic effects of N-hydroxy-1-amino-6-nitropyrene, 
      a partially reduced derivative of 1,6-dinitropyrene (1,6-DNP). The results were 
      compared with what was found previously in the same assay with 
      N-hydroxy-1-aminopyrene, the partially reduced derivative of 1-nitropyrene. The 
      shuttle vector plasmids were exposed to tritiated 1-nitro-6-nitrosopyrene for 1 h 
      in the presence of ascorbic acid, which served as a reducing agent to generate 
      N-hydroxy-1-amino-6-nitropyrene. 32P-Postlabeling showed that only a single 
      adduct was formed, i.e. N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene. There was a 
      linear increase in the number of adducts per plasmid as a function of applied 
      concentration and also in the frequency of supF mutants as a function of adducts 
      per plasmid, reaching 58.8 x 10(-4) above a background of 0.8 x 10(-4). When the 
      frequency of mutants induced when plasmids carrying residues of 1,6-DNP 
      replicated in the human cells was compared with that induced by 1-NP residues, 
      the former was 1.8 times more mutagenic than the latter. Both carcinogens induced 
      mainly base substitutions, primarily G.C----T.A transversions; but 1,6-DNP 
      adducts produced a significant fraction of -1 frameshifts, with most of these 
      located in a unique run of five Gs in the gene. Polymerase termination reactions 
      indicated that 1,6-DNP adducts were formed at every guanine, but not elsewhere in 
      the gene. The 'hot spots' for adduct formation were not perfectly correlated with 
      'hot spots' for mutation induction. This indicates that the ultimate biological 
      effect of the chemical depends not only on the number of adducts originally 
      formed, but also on such processes as cellular DNA repair, which may remove such 
      adducts from the plasmids before DNA replication occurs, as well as on the 
      structure of the neighboring bases at the site of the adduct.
FAU - Boldt, J
AU  - Boldt J
AD  - Department of Microbiology, Michigan State University, East Lansing 48824-1316.
FAU - Mah, M C
AU  - Mah MC
FAU - Wang, Y C
AU  - Wang YC
FAU - Smith, B A
AU  - Smith BA
FAU - Beland, F A
AU  - Beland FA
FAU - Maher, V M
AU  - Maher VM
FAU - McCormick, J J
AU  - McCormick JJ
LA  - eng
GR  - CA21253/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Mutagens)
RN  - 0 (Pyrenes)
RN  - 66Q2ZUF83N (1,6-dinitropyrene)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagens/*metabolism
MH  - Mutation
MH  - Plasmids
MH  - Pyrenes/*metabolism/toxicity
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 10.1093/carcin/12.1.119 [doi]
PST - ppublish
SO  - Carcinogenesis. 1991 Jan;12(1):119-26. doi: 10.1093/carcin/12.1.119.