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Titolo:
The mutagenic spectrum of acridine-linked aniline nitrogen mustards in AS52 cells: implications of DNA targeting with high selectivity for adenine orguanine bases
Autore:
Ferguson, LR; Turner, PM; Denny, WA;
Indirizzi:
Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc, Res Ctr, Auckland 1000, New Zealand Univ Auckland Auckland New Zealand 1000 Ctr, Auckland 1000, New Zealand
Titolo Testata:
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
fascicolo: 1, volume: 469, anno: 2000,
pagine: 115 - 126
SICI:
1383-5718(20000821)469:1<115:TMSOAA>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
APURINIC APYRIMIDINIC SITES; SEQUENCE SPECIFICITY; GENETIC TOXICOLOGY; ALKYLATING-AGENTS; INDUCED MUTATIONS; ESCHERICHIA-COLI; REPAIR; MELPHALAN; INSERTION; RESIDUES;
Keywords:
mutational spectra; DNA cross-linking; DNA adducts; nitrogen mustard; mutation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Ferguson, LR Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc, Res Ctr, Private Bag92019, Auckland 1000, New Zealand Univ Auckland Private Bag 92019 Auckland New Zealand 1000 nd
Citazione:
L.R. Ferguson et al., "The mutagenic spectrum of acridine-linked aniline nitrogen mustards in AS52 cells: implications of DNA targeting with high selectivity for adenine orguanine bases", MUT RES-GTE, 469(1), 2000, pp. 115-126

Abstract

The mutational spectra generated in AS52 cells at the gpt gene locus by aniline mustards were studied by the isolation of resistant clones and sequencing of the altered gene. A set of four aniline mustards (both mono- and bifunctional) linked to a DNA-affinic 9-aminoacridine (9-AA) carrier was used, together with the untargeted mustards chlorambucil (CHL) and its half-mustard, and the DNA binding carrier, 9-AA. Both 9-AA and CHL were weak cytotoxins, with the DNA-targeted mustards bring markedly (10-40-fold) more dose potent, and the bifunctional ones somewhat more toxic than the monofunctional ones. 9-AA produced a different spectrum of mutations to the spontaneousbackground, with more minor addition events and less base pair substitutions, and showing for the first time that frameshift events so characteristicof 9-AA in bacteria or bacteriophage: also occur in mammalian cells. The mutational spectra of the DNA-targeted mustards were quite different both fiom this and from the lesions caused by the untargeted mustards, which cause largely transition mutations at AT sites (despite a clear preference For formation of N-7-guanine adducts). There were very few transition mutations, suggesting that the initial O-6-alkylguanine/O-4-alkylthymine lesions considered to give ri se to these are relatively rare, There was also a lower incidence of complete deletions, usually attributed to DNA cross-links. Forthe short chain length targeted mustards, which form initial stable adducts largely (95%) at guanine N-7 sites, base pair substitution mutations, predominantly transversions, involved AT and GC base pairs equally. In contrast, the longer chain length targeted mustards, which Form > 90% of initial adducts at adenine N-1 sites, generated also formed transversion mutations, but these overwhelmingly (24/27) involved AT base pairs. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 13:13:04