DNA methylation during depleted uranium-induced leukemia.

Abstract Objectives The radioactive heavy metal depleted uranium (DU) is used in kinetic-energy penetrators in military applications. The objective of this study was to determine involvement of DNA methylation in DU-induced leukemia. Methods Methylation was measured by direct analysis of 5-methylcytosine content of spleen DNA in DU leukemic mice. Results Spleen hypomethylation occurred during DU-induced leukemogenesis (chronic internal DU exposure). Aberrant gene transcription was also detected. Conclusions Epigenetic mechanisms are implicated in DU-induced leukemia. These data are evidence of aberrant DNA hypomethylation being associated with DU leukemogenesis.