Heavy-Ion Radiobiology: New Approaches to Delineate Mechanisms Underlying Enhanced Biological Effectiveness

TLDR

Exposure to alpha‑particle emitters such as polonium and radium revealed deleterious biological effects, and the mechanisms underlying the heightened biological effectiveness of densely ionizing radiations—including alpha particles, neutrons, and heavy ions—remain an active area of investigation, especially as heavy‑ion and proton therapies gain popularity for their precise energy deposition and reduced normal‑tissue damage. The paper reviews recent advances in the radiobiology of densely ionizing radiations (heavy ions). The review covers advances in DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation, genomic instability, normal tissue radiobiology, and carcinogenesis, highlighting technical innovations such as pulsed‑field gel electrophoresis, FISH, linkage analysis, gene and protein expression studies, and the use of new cellular and animal systems with defined DNA repair deficiencies and epithelial models. The reviewed studies have significantly advanced understanding of heavy‑ion genotoxicity and tissue‑homeostasis effects, and their application in cancer therapy is also discussed.

Abstract

Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.