Cisplatin uptake

Hromas RA, North JA, Burns CP. Decreased cisplatin uptake by resistant L1210 leukemia cells. 

In more recent attempts to map the cellular distribution of cisplatin, Beretta et al. (50) incubated human ovarian cancer cells (A2780) with cisplatin concentrations of up to 100 xM for 30 minutes and observed electron dense spots, identified as large platinum deposits, distributed in the cell cytoplasm and nucleus. Additionally, it was observed that the platinum deposits made blunt contacts with the plasma membrane, which suggests that the cellular influx of cisplatin is through an endocytosis-independent manner that is consistent with the passive diffusion theory of cisplatin uptake (50). 

Pabla N et al (2009) The copper transporter Ctrl contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol 296(3) F505-F511... 

The mechanism of L-1210 resistance to cisplatin and other platinum antitumour agents remains to be clearly defined. Both Waud [77] and others [78] suggest that reduced cisplatin uptake may be responsible in part for the resistance of the cell line. It has also been found that glutathione levels are high in human ovarian carcinoma cells made resistant to cisplatin in vitro [79]. However, reduction in the level did not alter the resistance to the drug [80]. Decreases in amino-acid transport and changes in amino-acid substrate specificities have also been suggested as the basis for the resistance [81], but definitive evidence has been difficult to obtain. 

The process by which the kidney accumulates cisplatin is oxygen-dependent [10] and is competitively inhibited by drugs that are transported by the organic base system. Conversely, drugs that compete for the organic anion transport system, such as PAH and pyrazinoic acid, do not inhibit cisplatin uptake. Collectively, these observations indicate that the renal uptake of cisplatin involves transport or binding to components of the base transport system. 

Monitoring the Effects of Cisplatin Uptake in Rat Glioma Cells A Preliminary Study Using Fourier Transform Infrared Synchrotron Microspectroscopy... 

We postulate that FTIR spectroscopy in combination with a neural network algorithm shows potential as a rapid technique to monitor the eflects of cisplatin uptake and may have potential as a screening technique for a variety of... 

In order to explain why the asymmetric phosphodiester vibration is sensitive to cisplatin uptake it is important to understand the biochemical consequences... 

Regardless of the mechanism, FTIR spectroscopy shows potential as an independent modality to monitor the effects of cisplatin uptake in cells. The neural network model trained on cells from different cell lines, under different growth and instrumental conditions and tested on a independent data set, provides evidence that this could, in fact, be a tool to supplement conventional total cytosolic poly(A)-b mRNA and MTT assays. 

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