Immortalisation of a human diploid fibroblast cell strain: a DT-diaphorase paradox

Br J Cancer Suppl. 1996 Jul:27:S19-22.

Abstract

Transfection of a normal human diploid fibroblast cell strain, GM38, with a simian virus 40 (SV40) large T antigen containing plasmid, yielded an immortal cell line, G38-8X, which had a similar sensitivity as the parental cell strain to the quinone-containing chemotherapeutic agent mitomycin C (MMC), under both aerobic and hypoxic exposure conditions. The activity level of DT-diaphorase was similar in both the parental GM38 and G38-8X cells. Although DT-diaphorase could be detected by Western blot analysis, using two mouse anti-human monoclonal antibodies, in GM38 cells, it was not detected in the G38-8X cells. G38-8X cells have a slightly increased P450R activity (2-fold), and have elevated P-glycoprotein levels compared with the parental GM38 cell strain. The immortal G38-8X cell line is 2-fold more resistant to ionising radiation than the parental GM38 cell strain (D10 approximately 5 Gy). Although these SV40 large T antigen immortalised human diploid fibroblasts behaved similarly to their parental cell strain in terms of MMC sensitivity and DT-diaphorase activity, careful characterisation revealed that these cells had enhanced P-glycoprotein activity and had a decreased sensitivity to ionising radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Antigens, Polyomavirus Transforming / genetics
  • Cell Line
  • Cell Survival / drug effects
  • Fibroblasts / drug effects
  • Humans
  • Mice
  • Mitomycin / pharmacology*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Radiation Tolerance
  • Transfection

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Antigens, Polyomavirus Transforming
  • Mitomycin
  • NADPH-Ferrihemoprotein Reductase
  • NAD(P)H Dehydrogenase (Quinone)