A study of human small-cell lung carcinoma (hsclc) cell lines with different sensitivities to detect relevant mechanisms of cisplatin (cddp) resistance
✍ Scribed by G. A. P. Hospers; C. Meuer; L. De Leij; D. R. A. Uges; N. H. Mulder; E. G. E. De Vries
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- French
- Weight
- 687 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The cisplatin(CDDP)-resistant cell line GLC,-CDDP shows a variety of differences from the parent line GLC,. The aim of this study was to determine which of the observed changes correlated with the degree of resistance and was therefore relevant to the phenomenon of CDDP resistance. For these experiments we used cells of the sensitive hSCLC cell line GLC, and the in vitreacquired CDDP-resistant sublines GLC,-CDDP3 and GLC,-CDDPI I, with a resistance factor (RF) of 3 and I I respectively for CDDP and of 1.8 and 7.4 respectively for carboplatin. Carboplatin was used, in addition to CDDP in seeking relevant mechanisms. No consistency was found between the RF and the growth pattern or antigen expression, cellular volume, doubling time, cellular or nuclear platinum (Pt) content or the level of Pt-non-histone chromatin protein (NHCP) binding. A correlation was found between the RF and the level of glutathione (GSH), and a trend was found for the level of Pt-DNA binding, Pt-GG adduct content and the amount of interstrand cross-links (ISC). These changes might therefore be relevant for the development of resistance. These findings are compatible with a GSH-induced reduction of the amount of reactive Pt in the resistant cell, resulting in a lower net platination and toxic Pt-DNA adduct formation.