Occam’s broom and the dirty DSB: cytogenetic perspectives on cellular response to changes in track structure and ionization density

Abstract

Given equal doses, it is well-known that densely ionizing radiations are more potent in causing a number of biological effects compared to sparsely ionizing radiations, such as x- or gamma rays. According to classical models of radiation action, this results from differences in the spatial distribution of lesions along charged particle tracks. In recent years investigators have been barraged with the alternative narrative that this is instead due to ‘qualitative’ differences in the types of molecular lesions that each type of radiation produces. The present review discusses, mainly from a cytogenetic perspective, the merits and shortcomings of these seemingly contradictory viewpoints. There may be a kernel of truth to the idea that qualitative differences in the types of molecular lesions produced at the nanometer level affect RBE/LET relationships, but to ignore the fact that such differences result from longer-range spatial distributions of lesions produced along charged particle tracks is an unjustifiably narrow stance tantamount to employing Occam’s Broom. Not only are such spatial considerations indispensable in explaining the impact of ionization density upon higher-order biological endpoints, particularly chromosome aberrations, the explanations they provide render arguments based principally on the quality of IR damage largely superfluous.

Keywords:

• RBE
• LET
• chromosome aberrations
• clustered damage
• micrometer-scale damage

Acknowledgements

The author thanks Dr. Bradford Loucas and IJRB reviewers for their critical comments and careful reading of this paper, which was written as a tribute to Ray Meyn, a fine scientist, and a man not afraid of scientific controversy.

Disclosure statement

The author claims no conflict of interest, financial or otherwise, from research described in the manuscript.

Additional information

Funding

This work was funded by grant NNX15AG74G from the National Aeronautics and Space Administration (NASA).

Notes on contributors

Michael N. Cornforth

Michael N. Cornforth is an experimental radiation cytogeneticist whose interests lie in fundamental mechanisms of radiation damage at the chromosomal level, and its relationship to biophysical models of radiation action and DNA repair.