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

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)...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer. Supplement 1996-07, Vol.27, p.S19-S22
Main Authors: Kuehl, B L, Brezden, C B, Traver, R D, Siegel, D, Ross, D, Renzing, J, Rauth, A M
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - pharmacology
Antigens, Polyomavirus Transforming - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - analysis
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0306-9443