DECREASED ACCUMULATION AS A MECHANISM OF RESISTANCE TO CIS-DIAMMINEDICHLOROPLATINUM(II) IN HUMAN NON-SMALL-CELL LUNG-CANCER CELL-LINES - RELATION TO DNA DAMAGE AND REPAIR

  • 1 May 1990
    • journal article
    • research article
    • Vol. 50  (9) , 2549-2553
Abstract
The mechanism of resistance of cis-diamminedichloroplatinum(II) (CDDP) is still controversial, although several kinds of processes have been proposed. For elucidation of the mechanism of CDDP resistance in CDDP-resistant human non-small cell lung cancer cells (PC-9/0.5, 7.1-fold resistant), we examined the formation of DNA interstrand crosslinks (ICL), one kind of DNA damage induced by CDDP, its repair, and intracellular accumulation of CDDP. We measured the frequency of CDDP-induced ICL by means of the alkaline elution technique and the amount of intracellular platinum of intracellular accumulation of CDDP by means of atomic spectrophotometry in PC-9 (parental cell) and PC-9/0.5 cells. Formation of ICL in PC-9 cells exposed to 5 .mu.g of CDDP per ml for 6 h was 5.85 times that in PC-9/0.5 cells. On the other hand, the ability to repair CDDP-induced ICL was identical in both cell lines. Intracellular accumulation studies revealed that PC-9 retained 5.07 times as much platinum as that in PC-9/0.5 after 3-h exposure to CDDP. It was conjectured that the decrease in the intracellular accumulation of CDDP might be the main cause of CDDP resistance in PC-9 cells, since the decreased accumulation was paralleled by the decreased level of ICL.

This publication has 18 references indexed in Scilit: