Recent insights into the biological action of heavy-ion radiation

Biological effectiveness varies with the linear energy transfer (LET) of ionizing radiation. During cancer therapy or long-term interplanetary manned explorations, humans are exposed to high-LET energetic heavy ions that inactivate cells more effectively than low-LET photons like X-rays and gamma-rays. Recent biological studies have illustrated that heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, p53 mutations and intratumor hypoxia, and possess antiangiogenic and antimetastatic potential. Compared with heavy ions alone, the combination with chemical agents (a Bcl-2 inhibitor HA14-1, an anticancer drug docetaxel, and a halogenated pyrimidine analogue 5-iodo-2'-deoxyuridine) or hyperthermia further enhances tumor cell killing. Beer, its certain constituents, or melatonin ameliorate heavy ion-induced damage to normal cells. In addition to effects in cells directly targeted with heavy ions, there is mounting evidence for nontargeted biological effects in cells that have not themselves been directly irradiated. The bystander effect of heavy ions manifests itself as the loss of clonogenic potential, a transient apoptotic response, delayed p53 phosphorylation, alterations in gene expression profiles, and the elevated frequency of gene mutations, micronuclei and chromosome aberrations, which arise in nonirradiated cells having received signals from irradiated cells. Proposed mediating mechanisms involve gap junctional intercellular communication, reactive oxygen species and nitric oxide. This paper reviews briefly the current knowledge of the biological effects of heavy-ion irradiation with a focus on recent findings regarding its potential benefits for therapeutic use as well as on the bystander effect.