Bromodeoxyuridine induces p53-dependent and -independent cell cycle arrests in human gastric carcinoma cell lines

Dunfa Peng, Hiroyuki Sugihara, Takanori Hattori

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objectives: This study was designed to clarify the effects of bromodeoxyuridine (BrdU) on cell cycle progression and induction of apoptosis, and to demonstrate the role of P53 in these processes. Methods: We continuously exposed four human gastric carcinoma cell lines with different P53 status (P53 wild-type AGS and MKN-45, P53-mutated MKN-28 and P53-deleted KATO-III) to BrdU in asynchronous and synchronous culture conditions, and analyzed DNA histograms of apoptotic and nonapoptotic cells determined by static DNA cytofluorometry. Results: Continuous exposure to 20 μM BrdU after synchronization with hydroxyurea resulted in S phase delay and G1 arrest in MKN-45 and an increase of apoptosis in the first S/G2 phase in AGS and MKN-45. In the second S phase, a delay of 3-6 h was observed in all the four cell lines. In asynchronous cultures, continuous exposures to 20 and 200 μM BrdU for 72 h or more caused growth suppression with G1 and G2 arrests, respectively, in all the cell lines. Conclusions: These data suggested that the BrdU-induced growth suppression of the cell lines examined was mainly caused by cell cycle arrest rather than cell death, and that the cell cycle arrests in the first S and G1 phases (elicited by BrdU in the single DNA strand) and those in the second S, G2 and G1 phases (elicited by BrdU in the double DNA strands) were mediated by p53-dependent and -independent pathways, respectively.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalPathobiology
Volume69
Issue number2
DOIs
StatePublished - Dec 1 2001
Externally publishedYes

Fingerprint

Bromodeoxyuridine
Cell Cycle Checkpoints
Stomach
S Phase
Carcinoma
Cell Line
G2 Phase
DNA
G1 Phase
Apoptosis
Hydroxyurea
Growth
Cell Cycle
Cell Death

Keywords

  • Apoptosis
  • Bromodeoxyuridine
  • Cell cycle arrest
  • Cell lines
  • Human gastric carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Bromodeoxyuridine induces p53-dependent and -independent cell cycle arrests in human gastric carcinoma cell lines. / Peng, Dunfa; Sugihara, Hiroyuki; Hattori, Takanori.

In: Pathobiology, Vol. 69, No. 2, 01.12.2001, p. 77-85.

Research output: Contribution to journalArticle

@article{41d508baf51043ca8a02c2d33dcc6478,
title = "Bromodeoxyuridine induces p53-dependent and -independent cell cycle arrests in human gastric carcinoma cell lines",
abstract = "Objectives: This study was designed to clarify the effects of bromodeoxyuridine (BrdU) on cell cycle progression and induction of apoptosis, and to demonstrate the role of P53 in these processes. Methods: We continuously exposed four human gastric carcinoma cell lines with different P53 status (P53 wild-type AGS and MKN-45, P53-mutated MKN-28 and P53-deleted KATO-III) to BrdU in asynchronous and synchronous culture conditions, and analyzed DNA histograms of apoptotic and nonapoptotic cells determined by static DNA cytofluorometry. Results: Continuous exposure to 20 μM BrdU after synchronization with hydroxyurea resulted in S phase delay and G1 arrest in MKN-45 and an increase of apoptosis in the first S/G2 phase in AGS and MKN-45. In the second S phase, a delay of 3-6 h was observed in all the four cell lines. In asynchronous cultures, continuous exposures to 20 and 200 μM BrdU for 72 h or more caused growth suppression with G1 and G2 arrests, respectively, in all the cell lines. Conclusions: These data suggested that the BrdU-induced growth suppression of the cell lines examined was mainly caused by cell cycle arrest rather than cell death, and that the cell cycle arrests in the first S and G1 phases (elicited by BrdU in the single DNA strand) and those in the second S, G2 and G1 phases (elicited by BrdU in the double DNA strands) were mediated by p53-dependent and -independent pathways, respectively.",
keywords = "Apoptosis, Bromodeoxyuridine, Cell cycle arrest, Cell lines, Human gastric carcinoma",
author = "Dunfa Peng and Hiroyuki Sugihara and Takanori Hattori",
year = "2001",
month = "12",
day = "1",
doi = "10.1159/000048760",
language = "English (US)",
volume = "69",
pages = "77--85",
journal = "Pathobiology",
issn = "1015-2008",
publisher = "S. Karger AG",
number = "2",

}

TY - JOUR

T1 - Bromodeoxyuridine induces p53-dependent and -independent cell cycle arrests in human gastric carcinoma cell lines

AU - Peng, Dunfa

AU - Sugihara, Hiroyuki

AU - Hattori, Takanori

PY - 2001/12/1

Y1 - 2001/12/1

N2 - Objectives: This study was designed to clarify the effects of bromodeoxyuridine (BrdU) on cell cycle progression and induction of apoptosis, and to demonstrate the role of P53 in these processes. Methods: We continuously exposed four human gastric carcinoma cell lines with different P53 status (P53 wild-type AGS and MKN-45, P53-mutated MKN-28 and P53-deleted KATO-III) to BrdU in asynchronous and synchronous culture conditions, and analyzed DNA histograms of apoptotic and nonapoptotic cells determined by static DNA cytofluorometry. Results: Continuous exposure to 20 μM BrdU after synchronization with hydroxyurea resulted in S phase delay and G1 arrest in MKN-45 and an increase of apoptosis in the first S/G2 phase in AGS and MKN-45. In the second S phase, a delay of 3-6 h was observed in all the four cell lines. In asynchronous cultures, continuous exposures to 20 and 200 μM BrdU for 72 h or more caused growth suppression with G1 and G2 arrests, respectively, in all the cell lines. Conclusions: These data suggested that the BrdU-induced growth suppression of the cell lines examined was mainly caused by cell cycle arrest rather than cell death, and that the cell cycle arrests in the first S and G1 phases (elicited by BrdU in the single DNA strand) and those in the second S, G2 and G1 phases (elicited by BrdU in the double DNA strands) were mediated by p53-dependent and -independent pathways, respectively.

AB - Objectives: This study was designed to clarify the effects of bromodeoxyuridine (BrdU) on cell cycle progression and induction of apoptosis, and to demonstrate the role of P53 in these processes. Methods: We continuously exposed four human gastric carcinoma cell lines with different P53 status (P53 wild-type AGS and MKN-45, P53-mutated MKN-28 and P53-deleted KATO-III) to BrdU in asynchronous and synchronous culture conditions, and analyzed DNA histograms of apoptotic and nonapoptotic cells determined by static DNA cytofluorometry. Results: Continuous exposure to 20 μM BrdU after synchronization with hydroxyurea resulted in S phase delay and G1 arrest in MKN-45 and an increase of apoptosis in the first S/G2 phase in AGS and MKN-45. In the second S phase, a delay of 3-6 h was observed in all the four cell lines. In asynchronous cultures, continuous exposures to 20 and 200 μM BrdU for 72 h or more caused growth suppression with G1 and G2 arrests, respectively, in all the cell lines. Conclusions: These data suggested that the BrdU-induced growth suppression of the cell lines examined was mainly caused by cell cycle arrest rather than cell death, and that the cell cycle arrests in the first S and G1 phases (elicited by BrdU in the single DNA strand) and those in the second S, G2 and G1 phases (elicited by BrdU in the double DNA strands) were mediated by p53-dependent and -independent pathways, respectively.

KW - Apoptosis

KW - Bromodeoxyuridine

KW - Cell cycle arrest

KW - Cell lines

KW - Human gastric carcinoma

UR - http://www.scopus.com/inward/record.url?scp=0035669376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035669376&partnerID=8YFLogxK

U2 - 10.1159/000048760

DO - 10.1159/000048760

M3 - Article

C2 - 11752901

AN - SCOPUS:0035669376

VL - 69

SP - 77

EP - 85

JO - Pathobiology

JF - Pathobiology

SN - 1015-2008

IS - 2

ER -