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Titolo:
Mitomycin resistance in mammalian cells expressing the bacterial mitomycinC resistance protein MCRA
Autore:
Belcourt, MF; Penketh, PG; Hodnick, WF; Johnson, DA; Sherman, DH; Rockwell, S; Sartorelli, AC;
Indirizzi:
Yale Univ, Sch Med, Yale Canc Ctr, Dept Pharmacol, New Haven, CT 06520 USAYale Univ New Haven CT USA 06520 Dept Pharmacol, New Haven, CT 06520 USA Yale Univ, Sch Med, Yale Canc Ctr, Therapeut Radiol & Dev Therapeut Program, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 erapeut Program, New Haven, CT 06520 USA Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 robiol, Minneapolis, MN 55455 USA Univ Minnesota, Biol Proc Technol Inst, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 l Inst, Minneapolis, MN 55455 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 18, volume: 96, anno: 1999,
pagine: 10489 - 10494
SICI:
0027-8424(19990831)96:18<10489:MRIMCE>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAMSTER OVARY CELLS; COLON-CARCINOMA CELLS; DT-DIAPHORASE; STREPTOMYCES-LAVENDULAE; P-450 REDUCTASE; BIOACTIVATION; METABOLISM; DNA; CYTOTOXICITY; ANTIBIOTICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Sartorelli, AC Yale Univ, Sch Med, Yale Canc Ctr, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA Yale Univ 333 Cedar St New Haven CT USA 06520 CT 06520 USA
Citazione:
M.F. Belcourt et al., "Mitomycin resistance in mammalian cells expressing the bacterial mitomycinC resistance protein MCRA", P NAS US, 96(18), 1999, pp. 10489-10494

Abstract

The mitomycin C-resistance gene, mcrA, of Streptomyces lavendulae producesMCRA, a protein that protects this microorganism from its own antibiotic, the antitumor drug mitomycin C. Expression of the bacterial mcrA gene in mammalian Chinese hamster ovary cells causes profound resistance to mitomycinC and to its structurally related analog porfiromycin under aerobic conditions but produces little change in drug sensitivity under hypoxia. The mitomycins are prodrugs that are enzymatically reduced and activated intracellularly, producing cytotoxic semiquinone anion radical and hydroquinone reduction intermediates. Irt vitro, MCRA protects DNA from crosslinking by the hydroquinone reduction intermediate of these mitomycins by oxidizing the hydroquinone back to the parent molecule; thus, MCRA acts as a hydroquinone oxidase. These findings suggest potential therapeutic applications for MCRA in the treatment of cancer with the mitomycins and imply that intrinsic or selected mitomycin C resistance in mammalian cells may not be due solely to decreased bioactivation, as has been hypothesized previously, but instead could involve an MCRA-like mechanism.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 01:07:04