Quantitative mapping of platinum and essential trace metal in cisplatin resistant and sensitive human ovarian...

Platinum and trace metal distributions of a human ovarian adenocarcinoma cell line, IGROV1, and a subline resistant to the antitumor agent cisplatin were compared using nuclear microprobe analysis. The cisplatin-resistant cell line IGROV1-DDP exhibited a cytologically heterogeneous cell population. Two subpopulations were distinguished, small mononuclear cells, morphologically similar to the parental cells IGROV1, and enlarged polynuclear cells. Quantitative mapping of platinum and essential trace metal such as manganese, iron, copper and zinc was performed at the cellular level. Elemental maps were obtained with 2 mu m spatial resolution. Platinum appeared uniformly distributed within the cells, in all cell types. The same was true for copper and zinc. In some cases, iron maps showed preferential localization in the perinuclear region, especially in IGROV1-DDP polynuclear cells. Cisplatin resistance was associated with decreased platinum and iron concentrations and increased levels of copper and zinc. Decreased drug accumulation was encountered in both subpopulations of the resistant cell line. In contrast, high inter-individual variation of copper content was noticed in this cell line suggesting that in vitro cisplatin selection of human ovarian adenocarcinoma resistant cells can bring about the emergence of distinct cellular phenotypes.