The Bystander Response to Heavy-Ion Radiation: Intercellular Signaling Between Irradiated and Non-Irradiated Cells

Abstract

Ionizing radiation-induced bystander effect is the phenomenon whereby cells that are not themselves irradiated but received signals from directly irradiated cells exhibit biological responses. Human exposure to heavy-ion radiation occurs during manned space missions at the dose and dose rate much lower than those for cancer therapy. It should be noted herein that less irradiated cells coexist with more non-irradiated counterparts in a cell population exposed to a lower dose of radiation whose linear energy transfer is higher. The bystander effect should be thence examined to decipher the action mechanism of low-dose heavy ions. The bystander effect of heavy ions is manifested as inactivated clonogenic potential, a transient apoptotic response, delayed p53 phosphorylation, gene expression changes, a transient cell-cycle arrest, chromosome aberrations, elevated mutation frequency and micronucleation. Proposed underpinning mechanisms involve gap junctional intercellular communication and reactive oxygen/nitrogen species. This paper reviews briefly the current knowledge of the heavy ion-induced bystander effect.