Intracellular Distributions of the Anthracycline 4′-iodo-4′-deoxy-Doxorubicin and Essential Trace Metals Using Nuclear Microprobe Analysis

Abstract

The nuclear microprobe is an instrument of multi-elemental analysis with micro-imaging capabilities. Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS) were performed simultaneously on cultured cancer cells exposed to an antitumor agent, the anthracycline 4′-iodo-4′-deoxy-doxorubicin (IDX). Element mapping revealed that iodine and iron spatial distributions were strongly correlated, suggesting iron intracellular chelation by the anthracycline. Iron and iodine co-localizations were generally observed within the nucleus region. Quantitative determination of trace element concentrations shown that the average amount of endogenous trace metals did not change in cells after two hours exposure to 20 μM IDX. It suggests that no extra-cellular iron was imported into the cells during IDX uptake. From these results, it can be concluded that iron-IDX complexes might be formed in the intracellular space, at least when IDX is administered at 20 μM, and could participate to the various biological effects of anthracyclines antitumor drugs.