Role of p53 in growth suppression by bromodeoxyuridine in human gastric cancer cell lines

Guang Zhi Zuan, Hiroyuki Sugihara, Dun Fa Peng, Zhi Qiang Ling, Xiao Hong Yao, Kazusada Yoshitake, Takanori Hattori

Research output: Contribution to journalArticle

Abstract

Bromodeoxyuridine (BrdU) is known to cause base mispairs and DNA strand breaks during DNA synthesis, culminating in growth suppression. To know whether P53 gene plays any role in the BrdU-induced growth suppression, we continuously gave BrdU (20 μM) to the synchronized culture of human gastric cancer cell lines, MKN-45 (P53-wild type) and MKN-28 (P53-mutant), shortly after release from the G1/S block by hydroxyurea. In comparison with the control culture, the growth of MKN-28 was not suppressed until 48 hr of BrdU exposure, while that of MKN-45 was already suppressed at the 24 hr point. Continuous exposure to BrdU caused a S-phase delay and G2 arrest of around 6 hr each in MKN-45 and a delay only of the second S phase in MKN-28 in comparison with synchronized control cultures of matched cell cycle phase. BrdU-exposed MKN-45 cells showed a significantly higher incidence of apoptosis after the cells passed through the first G2 phase and the second S/G2 phases, but MKN-28 did not. It thus appears that the delays of S/G2 phases and an increased incidence of apoptosis in the first cell cycle are p53-dependent. The growth suppression in the second S/G2 phase or later observed in both of the cell lines may be p53-independent.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalActa Histochemica et Cytochemica
Volume33
Issue number6
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Bromodeoxyuridine
  • Cell cycle
  • Gastric cancer cell line
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Biochemistry
  • Physiology
  • Histology
  • Cell Biology

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