Enhanced nucleotide excision repair in cisplatin resistant human KB carcinoma cells

Motoi Mukai, Atsuko Kanzaki, Zhe Sheng Chen, Hitoshi Miyashita, Tomoyuki Sumizawa, Tatsuhiko Furukawa, Misako Haraguchi, Yuji Takebayashi, Hideo Takamatsu, Shin Ichi Akiyama

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

We previously reported that enhanced active efflux of cisplatin and increased GSH level were observed in KCP-4 cells. In the present study, KCP-4 cells were found to be cross-resistant to ultraviolet (UV) compared with parental KB-3-1 cells. Enhanced nucleotide excision repair (NER) was verified by time-dependent repair of UV-induced DNA damage. In addition, the amount of platinum bound to DNA after exposure to cisplatin decreased in a time-dependent manner in KCP-4 cells and this was reversed by aphidicolin, a DNA polymerase inhibitor. In stationary phase cultures, aphidicolin increased the sensitivity of KCP-4 cells to cisplatin. The expression of xeroderma pigmentosum complementation group F (XPF), an endonuclease involved in NER, was upregulated in KCP-4 cells. In KCP-4 cells the expression of hMSH6, one of the mismatch repair (MMR) factors, was decreased compared to parental KB-3-1 and revertant KCP-4R cells. However, KCP-4 cells were cross-resistant to oxaliplatin, and microsatellite instability was not observed in them. These findings suggest that the enhanced NER activity for DNA damage caused by cisplatin may be involved in cisplatin resistance in KCP-4 cells.

Original languageEnglish
Pages (from-to)839-844
Number of pages6
JournalOncology reports
Volume9
Issue number4
DOIs
Publication statusPublished - 2002 Jul

Keywords

  • Cisplatin resistance
  • Nucleotide excision repair

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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