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Titolo:
Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pH
Autore:
Yuan, JL; Narayanan, L; Rockwell, S; Glazer, PM;
Indirizzi:
Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 herapeut Radiol, New Haven, CT 06520 USA Yale Univ, Sch Med, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 ular & Dev Biol, New Haven, CT 06520 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 16, volume: 60, anno: 2000,
pagine: 4372 - 4376
SICI:
0008-5472(20000815)60:16<4372:DDRAEM>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
MURINE TUMOR-CELLS; MISMATCH REPAIR; GENETIC INSTABILITY; GLUCOSE STARVATION; EXCISION-REPAIR; CANCER; POLYMERASE; METABOLISM; MUTATION; PROTEIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Glazer, PM Yale Univ, Sch Med, Dept Therapeut Radiol, POB 208040, New Haven, CT 06520USA Yale Univ POB 208040 New Haven CT USA 06520 Haven, CT 06520USA
Citazione:
J.L. Yuan et al., "Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pH", CANCER RES, 60(16), 2000, pp. 4372-4376

Abstract

The tumor microenvironment is characterized by regions of fluctuating and chronic hypoxia, low pH, and nutrient deprivation. It has been proposed that this unique tissue environment itself may constitute a major cause of thegenetic instability seen in cancer. To In investigate possible mechanisms by which the tumor microenvironment might contribute to genetic instability, we asked whether the conditions found in solid tumors could influence cellular repair of DNA damage. Using an assay for repair based on host cell reactivation of UV-damaged plasmid DNA, cells exposed to hyposia and low pH were found to have a diminished capacity for DNA repair compared with control cells grown under standard culture conditions. In addition, cells cultured under hypoxia at pH 6.5 immediately after UV irradiation had elevated levels of induced mutagenesis compared with those maintained in standard growth conditions. Taken together, the results suggest that cellular repair functions mag be impaired under the conditions of the tumor microenvironment, causing hypermutability. to DNA damage, This alteration in repair capacity may constitute an important mechanism underlying the genetic instability of cancer cells in vivo.

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Documento generato il 23/09/20 alle ore 15:27:55