PARTIAL CHARACTERIZATION OF A CISPLATIN-RESISTANT SUBLINE OF MURINE RIF-1 TUMOR-CELLS

Citation
A. Mansouri et al., PARTIAL CHARACTERIZATION OF A CISPLATIN-RESISTANT SUBLINE OF MURINE RIF-1 TUMOR-CELLS, International journal of oncology, 7(3), 1995, pp. 649-656
Citations number
35
Categorie Soggetti
Oncology
ISSN journal
10196439
Volume
7
Issue
3
Year of publication
1995
Pages
649 - 656
Database
ISI
SICI code
1019-6439(1995)7:3<649:PCOACS>2.0.ZU;2-8
Abstract
We have developed a drug-resistant cell line (RIF/Ptr1) (R) from the m urine radiation-induced fibrosarcoma (RIF-1) also designated Pts or (S ). This subline has been characterized previously by an increased resi stance to cisplatin (cis-diamminedichloroplatinum(II) or CDDP), lowere d intracellular CDDP concentrations, and elevated intracellular glutat hione (GSH) levels (1.4-2.5-fold) but unaltered formation of CDDP-DNA interstrand cross-links. In this work, we have shown that RIF/Ptr1 cel ls were also resistant to carmustine (BCNU) and X-irradiation. Neither cell line had P-glycoprotein 170. The intrastrand CDDP-DNA adduct lev el was proportional to the concentration of intracellular CDDP. The ox ygen consumption, ATP level, and glycolysis were similar in both cell lines. The cisplatin influx and efflux showed that the RIF/Ptr1 cells had lower drug influx and higher drug efflux compared to RIF-1. We con clude that the major difference between the cisplatin sensitive and ci splatin-resistant cells in this model is the regulation of cisplatin t ransport probably at the cell membrane level suggesting that a membran e active transport system other than P-glycoprotein 170 is involved. W hether glutathione is linked to the putative membrane transporter need s further investigation.