Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
EFFECT OF PYRAZOLOACRIDINE (NSC-366140) ON DNA TOPOISOMERASE-I AND TOPOISOMERASE-II
Autore:
ADJEI AA; CHARRON M; ROWINSKY EK; SVINGEN PA; MILLER J; REID JM; SEBOLTLEOPOLD J; AMES MM; KAUFMANN SH;
Indirizzi:
MAYO CLIN & MAYO FDN,DIV ONCOL RES,1301 GUGGENHEIM,200 1ST ST SW ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DIV ONCOL RES ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DIV MED ONCOL ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,SCH MED,DEPT PHARMACOL ROCHESTER MN 55905 JOHNS HOPKINS UNIV,CTR ONCOL BALTIMORE MD 21287 WARNER LAMBERT PARKE DAVIS ANN ARBOR MI 48105
Titolo Testata:
Clinical cancer research
fascicolo: 3, volume: 4, anno: 1998,
pagine: 683 - 691
SICI:
1078-0432(1998)4:3<683:EOP(OD>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTITUMOR AGENT; ACTINOMYCIN-D; SOLID TUMORS; CELL-LINE; PHASE-I; INHIBITION; CAMPTOTHECIN; RESISTANCE; ADRIAMYCIN; CLEAVAGE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
A.A. Adjei et al., "EFFECT OF PYRAZOLOACRIDINE (NSC-366140) ON DNA TOPOISOMERASE-I AND TOPOISOMERASE-II", Clinical cancer research, 4(3), 1998, pp. 683-691

Abstract

Pyrazoloacridine (PA), an acridine congener with an unknown mechanismof action, has shown selective activity against solid tumor cells, cytotoxicity in noncycling and hypoxic cells, and promising antitumor activity in Phase I clinical trials, In the present study, the effect ofPA on topoisomerase (topo) activity was evaluated using yeast strainslacking functional topo I or II, mammalian cell nuclear extracts, purified samples of mammalian topo I and topo II, and intact mammalian tissue culture cells, Clonogenic assays revealed that PA cytotoxicity inyeast strains was unaffected by selective loss of topo I or topo II activity, On the other hand, enzyme assays revealed that 2-4 mu M PA abolished the catalytic activity of both topo I and topo IT in vitro, Incontrast to topotecan and etoposide, PA did not stabilize covalent topo-DNA complexes, Instead, PA inhibited topotecan-induced stabilization of covalent topo I-DNA complexes and etoposide-induced stabilizationof topo II-DNA complexes ill vitro and in intact cells, Consistent with these results, colony-forming assays indicated that shortterm PA exposure inhibited the cytotoxicity of topotecan and etoposide, whereas prolonged PA exposure was itself toxic to these cells, Accumulation studies revealed that PA was concentrated as much as 250-fold in drug-treated cells, resulting in intranuclear concentrations that far exceeded those required to inhibit topo I and topo II, Collectively, these results not only suggest that PA can target both topo I and topo II at clinically achievable concentrations but also indicate that its mechanism is distinct from topo I and topo II poisons presently licensed for clinical use.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:30:28