HEAVY-ION RADIOBIOLOGY - NEW APPROACHES TO DELINEATE MECHANISMS UNDERLYING ENHANCED BIOLOGICAL EFFECTIVENESS

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 effec ts. The mechanisms underlying the increased biological effectiveness o f densely ionizing radiations, including or particles, neutrons and hi ghly energetic heavy charged particles, remain an active area of inves tigation. 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 repa ir, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogene sis in vivo. We focus on technical innovations, including novel applic ations of pulsed-field gel electrophoresis, fluorescence in situ hybri dization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and anim al systems, including those with defined DNA repair deficiencies, as w ell as epithelial cell model systems to assess neoplastic transformati on both in vitro and in vivo. The studies reviewed herein have had a s ubstantial impact on our understanding of the genotoxic effects of hea vy ions as well as their distinct effects on tissue homeostasis. The u se of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several center s around the world, due to their unique energy deposition characterist ics that enhance the therapeutic effect and help reduce damage to norm al tissue. (C) 1998 by Radiation Research Society.