ESTABLISHMENT OF A CISPLATIN-RESISTANT GASTRIC-CARCINOMA CELL-LINE OCUM-2M DDP/

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric canc er cell line, OCUM-2M/DDP, was established by chronic exposure of cell s of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP a t progressively increasing concentrations. The OCUM-2M/DDP cell line h ad an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromoso me number and DNA index, suggesting that some alterations of the DNA i n the CDDP-resistant cells had occur-red. Neither the parent nor resis tant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, t he intracellular platinum content of OCUM-2M cells was significantly h igher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng /mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cel ls and OCUM-2M/DDP cells were 3.5 +/- 1.0 mu g/mg protein and 16.8 +/- 1.2 mu g/mg protein, respectively. These levels were also significant ly different. These findings suggest that the possible mechanisms of a cquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in i ntracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/D DP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.