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 sensitive parental cell line (normal) and a cisplatin resistant derivative were tested for their cisplatin responses and expression for three reputed mechanisms of resistance. In each case, the derivative cell lines showed resistance to cisplatin when treated either in exponential or plateau growth phase. For both the resistant and the normal cell line there was greater resistance to cisplatin treatment when cells were treated in exponential growth phase. Mechanisms of resistance were expressed in all three resistant variants. The cervical carcinoma resistant variant expressed higher GSH levels and lower cisplatin uptake levels but not elevated polymerase levels. The other two variant cell lines for 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 change 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.