Genomic Instability and Carcinogenesis of Heavy Charged Particles Radiation: Clinical and Environmental Implications.

Keywan Mortezaee,Dheyauldeen Shabeeb,Bagher Farhood,Masoud Najafi,Amirhossein Ahmadi,Ahmed Eleojo Musa

doi:10.3390/medicina55090591

Abstract

One of the uses of ionizing radiation is in cancer treatment. The use of heavy charged particles for treatment has been introduced in recent decades because of their priority for deposition of radiation energy in the tumor, via the Bragg peak phenomenon. In addition to medical implications, exposure to heavy charged particles is a crucial issue for environmental and space radiobiology. Ionizing radiation is one of the most powerful clastogenic and carcinogenic agents. Studies have shown that although both low and high linear energy transfer (LET) radiations are carcinogenic, their risks are different. Molecular studies have also shown that although heavy charged particles mainly induce DNA damage directly, they may be more potent inducer of endogenous generation of free radicals compared to the low LET gamma or X-rays. It seems that the severity of genotoxicity for non-irradiated bystander cells is potentiated as the quality of radiation increases. However, this is not true in all situations. Evidence suggests the involvement of some mechanisms such as upregulation of pro-oxidant enzymes and change in the methylation of DNA in the development of genomic instability and carcinogenesis. This review aimed to report important issues for genotoxicity of carcinogenic effects of heavy charged particles. Furthermore, we tried to explain some mechanisms that may be involved in cancer development following exposure to heavy charged particles.

Highlights

For many years, the use of heavy charged particles has been proposed for clinical cancer therapy because of their biophysical properties
An increased level of nitric oxide (NO) generation and reduced mitochondrial membrane potential, as well as upregulation of NADPH oxidase, were more obvious for mice irradiated with iron particles [46]
One of the important mechanisms of genomic instability and increased risk of carcinogenesis is a change in epigenetic modulators that affect DNA methylation

Summary

Introduction

The use of heavy charged particles has been proposed for clinical cancer therapy because of their biophysical properties. The use of protons and heavier particles were. There is a growing number of centers using particle radiotherapy. The main factor behind the use of heavy charged particles is their interesting biophysical properties which cause lower radiation dose deposition in surrounding normal tissues while delivering most of its energy to the tumor [3].

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