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Titolo:
DETERMINATION OF DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOL SIZES IN RIBONUCLEOTIDE REDUCTASE CDNA TRANSFECTED HUMAN KB CELLS
Autore:
ZHOU BS; KER R; HO R; YU J; ZHAO YR; SHIH J; YEN Y;
Indirizzi:
CITY HOPE NATL MED CTR,DEPT MED ONCOL,1500 E DUARTE RD DUARTE CA 91010 CITY HOPE NATL MED CTR,DEPT MED ONCOL DUARTE CA 91010
Titolo Testata:
Biochemical pharmacology
fascicolo: 10, volume: 55, anno: 1998,
pagine: 1657 - 1665
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-LYMPHOMA CELLS; WILD-TYPE; HYDROXYUREA; SUBUNIT; M2; CYCLE; EXPRESSION; RESISTANCE; MUTANT; ASSAY;
Keywords:
RIBONUCLEOTIDE REDUCTASE; DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOLS; HYDROXYUREA; DRUG RESISTANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
B.S. Zhou et al., "DETERMINATION OF DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOL SIZES IN RIBONUCLEOTIDE REDUCTASE CDNA TRANSFECTED HUMAN KB CELLS", Biochemical pharmacology, 55(10), 1998, pp. 1657-1665

Abstract

Ribonucleotide reductase (RR) is a rate-limiting enzyme in DNA synthesis, which is responsible for controlling deoxyribonucleoside triphosphate (dNTP) pool size. It has been shown that transfection of RR M2 cDNA in human KB cells (M2-D clone) results in overexpression for the M2subunit and resistance to hydroxyurea (HU). In this study, dNTP pool assays were performed to measure the pool sizes in six cell lines: twocontrols, three transfectants, and drug-induced HU-resistant (HUR) cells. Total dNTP levels among the six tell lines rose in the following order: KB wild-type, KB vector-only transfectant, M1 cDNA transfectant, M2 cDNA transfectant, M1/M2 cDNA transfectant, and HU-induced resistant clone. The dCTP levels of the cells mimicked the total dNTP pools on a smaller scale. The significant increases in the dCTP pool sizes of the M2-D, X-D, and HUR clones were proportional to their respective increases in RR activity. Relative to all other transfectants, the M1-D clone demonstrated lower dCTP levels but increased dATP pools. The M1-D clone demonstrated a significant resistance to dNTP inhibition of RR activity compared with the control KB wild-type cells. In contrast,a profound inhibition of dCTP and a decreased sensitivity to dATP inhibition was observed in M2-D, X-D, and HUR clones. In summary, M2 cDNAtransfectants and HUR clones had increased RR activity as well as expanded dNTP pools, particularly dCTP, when compared with wild-type KB cells. These data provide evidence for the intertwined relationship between RR activity and dNTP pools. (C) 1998 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 18:50:29