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
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.