PLoS ONE (Jan 2013)

Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.

  • Qi Wang,
  • Kangping Cui,
  • Osvaldo Espin-Garcia,
  • Dangxiao Cheng,
  • Xiaoping Qiu,
  • Zhuo Chen,
  • Malcolm Moore,
  • Robert G Bristow,
  • Wei Xu,
  • Sandy Der,
  • Geoffrey Liu

DOI
https://doi.org/10.1371/journal.pone.0082363
Journal volume & issue
Vol. 8, no. 12
p. e82363

Abstract

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BackgroundTo establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines.ResultsCompared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352%) in BLM-resistant sub-clones (pConclusionBleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis.