Ultrastructural changes in the mouse heart after chronic DOX treatment. TEM images of ultrathin sections of mouse hearts from saline-treated (A-B) and DOX-treated (C-E), nonsurviving wild-type (C), Hfe^-/- (D), and heterozygous Hfe^+/- (E) mice. Damaged mitochondria and electron-dense particles (magnified inset, D-E) are evident in DOX-treated mice (arrows). Original magnifications: × 5000 (A-E); × 25 000 (insets). (F) Analysis of the particles by energy-dispersive X-ray microanalysis in nonosmicated ultrathin sections obtained from the heart tissue from the same mouse shown in panel D. EDS spectra from background (top panel) and particles (bottom panel). Cl (chlorine) and Cu (copper) were detected in all samples; Fe (iron) was detected exclusively in the particles.