Studies have shown that radiation exposure affects global gene expression in mammalian cells. However, little is known about the effects of HZE particles on gene expression. To study these effects, human skin fibroblasts were irradiated with HZE particles of different energies and LETS. The data obtained from these experiments indicate that changes in gene expression are dependent on the energy of the radiation source. Particles with the highest energy, i.e. iron, induced the biggest expression changes in terms of numbers of genes and magnitudes of changes. Many genes were found to undergo significant expression changes after HZE-particle irradiation, including CDKN1A/p21, MDM2, TNFRSF6/fas, PCNA and RAD52. Unlike X rays, HZE particles expose cells to two types of radiation: primary ions and 8 rays. We hypothesized that the biological effects of 6 rays, which are secondary electron emissions, should resemble the effects of X rays. To explore this idea, gene expression changes between cells that had been irradiated with HZE particles and X rays were compared. The results support our hypothesis since the number of genes that commonly changed after exposure to both radiations increased as a function of particle energy. (c) 2005 by Radiation Research Society.