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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
33
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pubmed:dateCreated |
1997-9-15
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pubmed:abstractText |
Mutations induced by the (+)-anti diol epoxide of benzo[a]pyrene [(+)-anti-B[a]PDE] were described previously in the supF gene of the Escherichia coli plasmid pUB3 [Rodriguez et al.(1993) Biochemistry, 32, 1759]. (+)-anti-B[a]PDE induced a complex pattern of mutations, including insertions, deletions, frameshifts, as well as base substitution mutations, which for G:C base pairs alone included a significant fraction of G:C --> T:A, A:T and C:G mutations. A variety of results suggest that most of these mutations arise from the major adduct ([+ta]-B[a]P-N2-dG), raising the question how can a single adduct induce different kinds of mutations? Our working hypothesis in this regard is that (1) an adduct can adopt multiple conformations; (2) different conformations cause different mutations; and (3) adduct conformation is controlled by various factors, such as DNA sequence context. To investigate what conformation is associated with what mutation, it is essential to find examples where [+ta]-B[a]P-N2-dG induces principally one kind of mutation as a prelude to the study in that same context of the conformation(s) potentially relevant to mutagenesis. Earlier work indicated that (+)-anti-B[a]PDE gave a preponderance of G --> A mutations in a 5'-CGT-3 sequence context, and herein it is shown that these mutations are likely to be attributable to the major adduct, since in this same sequence context [+ta]-B[a]P-N2-dG studied site specifically also induces principally G --> A mutations ( approximately 82%). Previously, [+ta]-B[a]P-N2-dG was shown to induce principally G --> T mutations (approximately 97%) in a 5'-TGC-3' sequence context. Thus, by simply altering its surrounding sequence context this adduct can give a preponderance of either G --> A or G --> T mutations. This is the most dramatic change in base substitution mutagenic specificity for an adduct described to date and illustrates that the qualitative pattern of mutagenesis by a bulky adduct can be remarkably diverse.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7,8-Dihydro-7,8-dihydroxybenzo(a)pyr...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Transfer,
http://linkedlifedata.com/resource/pubmed/chemical/benzo(a)pyrene-7,8-dihydrodiol-9,10-...,
http://linkedlifedata.com/resource/pubmed/chemical/supF tRNA
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10256-61
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9254624-7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide,
pubmed-meshheading:9254624-Chromatography, High Pressure Liquid,
pubmed-meshheading:9254624-DNA Adducts,
pubmed-meshheading:9254624-Genes, Suppressor,
pubmed-meshheading:9254624-Mutagenesis,
pubmed-meshheading:9254624-Mutagens,
pubmed-meshheading:9254624-Mutation,
pubmed-meshheading:9254624-Plasmids,
pubmed-meshheading:9254624-RNA, Transfer
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pubmed:year |
1997
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pubmed:articleTitle |
The major, N2-dG adduct of (+)-anti-B[a]PDE shows a dramatically different mutagenic specificity (predominantly, G --> A) in a 5'-CGT-3' sequence context.
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pubmed:affiliation |
Department of Biology, Boston University, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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