Using X-ray absorption spectroscopy and microprobe synchrotron radiation-X-ray fluorescence imaging for understanding the mode of action of arsenic anti-leukaemia agents

Abstract

Despite its reputation as a poison, arsenic is also a highly effective anti-leukaemia agent. In order to improve on its efficacy, a better understanding of the metabolism of arsenic, including the formation of specific arsenic metabolites, is necessary. In this study XAS was used to gain an understanding of the metabolism of arsenic in human hepatoma cells and microprobe SR-XRF imaging was used to determine potential targets for the identified arsenic species. It was found that the toxic arsenic metabolites, [MMAIII(GS)2] and [DMAIII(GS)], were produced in human cells and that these metabolites potentially interact with DNA or, more probably, proteins associated with DNA transcription. © 2012 Taylor & Francis Group.