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A cisplatin (CDDP)-resistant human osteosarcoma cell line (OST/R) was established by continuous exposure to CDDP. OST/R cells proved to be 6.73 times more resistant to CDDP compared with parental OST cells, and showed cross-resistance to carboplatin (CBDCA). The mechanism of CDDP resistance was a significant decrease of intracellular platinum accumulation which was 40% of that in OST cells. OST/R cells were exposed to CDDP for 6 hours, the platinum was released from the cytoplasm of OST/R cells without reaching a state of equilibrium. DNA synthesis in OST/R cells was not inhibited by CDDP exposure, while in OST cells it was reduced by 50%. These data provide the first evidence that the increased efflux of platinum may play an important role in CDDP-resistance.
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