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Titolo:
COMPARATIVE MUTATIONAL SPECTRA OF THE NITROGEN-MUSTARD CHLORAMBUCIL AND ITS HALF-MUSTARD ANALOG IN CHINESE-HAMSTER AS52 CELLS
Autore:
YAGHI BM; TURNER PM; DENNY WA; TURNER PR; OCONNOR CJ; FERGUSON LR;
Indirizzi:
UNIV AUCKLAND,FAC MED & HLTH SCI,CANC RES LAB,PRIVATE BAG 92019 AUCKLAND 1000 NEW ZEALAND UNIV AUCKLAND,FAC MED & HLTH SCI,CANC RES LAB AUCKLAND 1000 NEW ZEALAND
Titolo Testata:
Mutation research. Fundamental and molecular mechanisms of mutagenesis
fascicolo: 1-2, volume: 401, anno: 1998,
pagine: 153 - 164
SICI:
1386-1964(1998)401:1-2<153:CMSOTN>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
APURINIC APYRIMIDINIC SITES; GENETIC TOXICOLOGY; ESCHERICHIA-COLI; ADENINE ADDUCTS; DNA-SYNTHESIS; MITOMYCIN-C; BASE-PAIRS; AGENTS; SEQUENCE; MUTAGENESIS;
Keywords:
MUTATIONAL SPECTRUM; DNA CROSS-LINKING; DNA ADDUCT; CHLORAMBUCIL; CHLORAMBUCIL HALF-MUSTARD; NITROGEN MUSTARD; MICRONUCLEUS; MUTATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
B.M. Yaghi et al., "COMPARATIVE MUTATIONAL SPECTRA OF THE NITROGEN-MUSTARD CHLORAMBUCIL AND ITS HALF-MUSTARD ANALOG IN CHINESE-HAMSTER AS52 CELLS", Mutation research. Fundamental and molecular mechanisms of mutagenesis, 401(1-2), 1998, pp. 153-164

Abstract

Nitrogen mustards play an important role in current cancer chemotherapy, The most effective antitumour agents are those carrying two alkylating functions, probably through their ability to form interstrand cross-links in DNA, Such lesions appear to create more of a block in DNA replication and are more difficult to repair than are most monoadducts. Although there were early reports that monofunctional drugs were more mutagenic than the bifunctional drugs, this has not been formally proved using structurally related drugs in a mutagenicity assay capable of detecting a range of different events. We have studied both the mutagenic potency and spectrum of events caused by treatment with the clinical agent, chlorambucil, compared with its half-mustard analogue, inChinese hamster ovary (CHO)-AS52 cells. Although both drugs caused comparable increases in mutation frequency at doses killing 90% of cells(from around 9 x 10(-6) to around 9 x 10(-5) mutant cells), the nature of events differed significantly between the drugs. By far the majority of mutations caused by the half-mustard were transversion mutations, and almost all of these could be interpreted in relation to the DNAadducts that are known to be formed. In contrast, the majority of chlorambucil-induced mutations were major deletions, and point mutations were only identified from a few clones. Parallel micronucleus assays verified that chlorambucil has a stronger ability to break chromosomes than the half-mustard. These two drugs are thought to form similar monoadducts, but only the full mustard can form interstrand cross-links. The data suggest that DNA cross-links, although only a minor fraction of the total lesions, dominate the mutagenic spectrum and lead to gross changes at the chromosome level that can not be readily associated with individual lesions produced by the drug. (C) 1998 Elsevier ScienceB.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 11:19:49