ANALYSIS OF MECHANISMS OF CISPLATIN RESISTANCE IN 3 PAIRS OF HUMAN TUMOR-CELL LINES EXPRESSING NORMAL AND RESISTANT RESPONSES TO CISPLATIN

Three pairs of human tumour cell Lines each having a cisplatin sensiti ve parental cell line (normal) and a cisplatin resistant derivative we re tested for their cisplatin responses and expression for three reput ed mechanisms of resistance. In each case, the derivative cell lines s howed resistance to cisplatin when treated either in exponential or pl ateau growth phase. For both the resistant and the normal cell line th ere was greater resistance to cisplatin treatment when cells were trea ted in exponential growth phase. Mechanisms of resistance were express ed in all three resistant variants. The cervical carcinoma resistant v ariant expressed higher GSH levels and lower cisplatin uptake levels b ut not elevated polymerase levels. The other two variant cell lines fo r the glioma and the lung cancer expressed all three of the mechanisms (increased GSH, decreased cisplatin uptake and increased polymerases) associated with resistance. There was no correlation to the level of resistance expressed and the number of mechanisms expressed but the ch ange in response of the parental line to becoming a resistant variant may be related to the basal level of expression of some of the factors that are associated with resistance.