Having identified dicyanogold(I) as a common metabolite of gold-based antiarthritis drugs, we are investigating the effects of the compound on the production of lymphokines. Handel, et al. 1 suggested that the transcription factor AP-1, critical to the production of a number of cytokines, might be the target for gold compounds because of a critical cysteine within its DNA binding region. Using Jurkat cells, an established cell line as a model for CD4(+) lymphocytes, we have shown that dicyanogold inhibits the binding of AP-1 to DNA and inhibits the synthesis of IL-2 mRNA and protein. In a macrophage line, THP-1, which synthesizes IL-1beta in response to mitogen, we have shown that dicyanogold inhibits the binding of a second transcription factor, CREB to DNA. Incubation of THP-1 cells with dicyanogold inhibits the production of IL-1beta mRNA. These results suggest that the mechanism of action of gold drugs may be through their interaction with transcription factors necessary for the immune activation seen in Rheumatoid Arthritis.

A sensitive method is described for measuring cisplatin and some possible metabolites. The method combines reversed-phase ion-pairing liquid chromatography (LC) with inductively coupled plasma mass spectrometry (ICP-MS) for platinum-specific detection. Separation conditions for cisplatin hydrolysis products and the reaction products of cisplatin with methionine, cysteine, and glutathione have been investigated with sodium dodecylsulfate or heptanesulfonate as the ion-pairing agent. The detection limit for cisplatin was found to be 0.1 ng, corresponding to a concentration detection limit of 1 ng/ml when using an injection volume of 100 μl. This study has demonstrated the usefulness of LC—ICP-MS for cisplatin metabolism studies.