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Titolo:
Spontaneous mutation spectra in supF: comparative analysis of mammalian cell line base substitution spectra
Autore:
Lewis, PD; Harvey, JS; Waters, EM; Skibinski, DOF; Parry, JM;
Indirizzi:
Univ Coll Swansea, Sch Biol Sci, Ctr Mol Genet & Toxicol, Bioniformat Lab,Swansea SA2 8PP, W Glam, Wales Univ Coll Swansea Swansea W Glam Wales SA2 8PP sea SA2 8PP, W Glam, Wales
Titolo Testata:
MUTAGENESIS
fascicolo: 6, volume: 16, anno: 2001,
pagine: 503 - 515
SICI:
0267-8357(200111)16:6<503:SMSISC>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
SHUTTLE VECTOR PLASMID; INDUCED POINT MUTATIONS; ESCHERICHIA-COLI; TRANSGENIC MICE; MONKEY CELLS; DNA-REPAIR; GENE; SPECIFICITY; MUTAGENESIS; TISSUE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Lewis, PD Univ Coll Swansea, Sch Biol Sci, Ctr Mol Genet & Toxicol, Bioniformat Lab,Swansea SA2 8PP, W Glam, Wales Univ Coll Swansea Swansea W Glam Wales SA2 8PP P, W Glam, Wales
Citazione:
P.D. Lewis et al., "Spontaneous mutation spectra in supF: comparative analysis of mammalian cell line base substitution spectra", MUTAGENESIS, 16(6), 2001, pp. 503-515

Abstract

The last decade has seen a dramatic accumulation of mutation data from reporter genes utilized in mutagenesis experiments involving DNA reactive agents allowing comparisons for the mutagenic potential between many different mutagens. When analysing chemically induced mutation spectra it is important to establish the potential spontaneous background before drawing conclusions concerning specific chemically induced hotspots. A major mutation reporter system gene used in mammalian cells is the supF suppressor tRNA gene. The Mammalian Gene Mutation Database (MGMD) contains a considerable number of supF spontaneous mutations permitting a thorough analysis of spontaneous mutations in mammalian cell lines from different species and tissues. Analyses of spontaneous mutation spectra were performed using a range of statistical techniques. Spontaneous mutations were observed at 82.4% of the nucleotides in the supF suppressor tRNA sequence although the pattern of significant hotspots differed between cell lines. Our analyses of spontaneous mutation spectra show considerable variation both within and between cell lines for the distributions of spontaneous mutations occurring with no clear tissue or species-specific patterns emerging. In addition, spectra derived fromsupF recovered from liver and skin of transgenic mice, were similar to each other, but showed significant differences from many in vitro spectra. Themost common base substitutions were G:C>TA transversions and G:C>A:T transitions, although levels of each type differed between cell lines. There wasalso variation between cell lines for the most mutable dinucleotides, however, significant hotspots were frequently observed at CpG sites and sequences containing GG/CC. We conclude that the number of varying distributions and potential hotspots for spontaneous mutations should thus be considered when comparing chemically induced mutation spectra in supF. The spectra presented here will be a useful reference for analysis and re-analysis of chemically induced spectra as well as for use in comparison with the spontaneousspectra of other gene systems.

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Documento generato il 24/01/20 alle ore 12:16:00