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

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.

Orange peels and Chlorella vulgaris supplementation ameliorate gamma radiation‐induced oxidative stress by regulating TGF‐β and NOX2/NOX4 signaling pathways

“…76 NOX4, resulting in the repetitive generation of free radicals, 77,78 causing oxidative stress, genomic instability, inflammation, carcinogenesis, and other ionizing radiation implications. 79,80 Supplementation with orange peels and C. vulgaris resulted in a significant decrease in expression, as shown in Figure 1; in agreement with data obtained by Chaudhari and Baviskar 81 and Maneesai et al 82 who found that C. vulgaris or orange peels supplementation suppressed NOS pathway and inhibited pro-inflammatory cytokines through COX and suppressed inflammation.…”

Protective Potentials of Alpha-Lipoic Acid against Ionizing Radiation-Induced Brain Damage in Rats

“…NOX2 and NOX4 are among the most important NADPH oxidase subfamilies. It has been reported that the activation and upregulation of these enzymes are associated with oxidative stress, DNA damage, genomic instability, and cell death for a long time after exposure to the ionizing radiation [55,58]. Furthermore, there is a growing evidence that confirms the pivotal role of these enzymes in neurodegenerative diseases [60].…”

“…Experimental studies in the recent decade have indicated a key role of reduction/oxidation (redox) interactions in chronic oxidative stress, inflammation, and normal tissue injury [54]. The main redox system mediators are NADPH oxidases, cyclooxygenase-2, inducible nitric oxide synthase, mitochondria, and antioxidant defense enzymes [55][56][57][58]. Overproduction of ROS by mitochondria and prooxidant enzymes like NOX2 and NOX4 can suppress the activity of antioxidant defense enzymes, leading to cell death and tissue injury [59].…”

The Footprint of Exosomes in the Radiation-Induced Bystander Effects

“…Moreover, it was found that high LET radiation induced more damage in bystander cells, with an increased number of micronuclei formation compared to low LET radiation. These effects are associated with an increase in ROS production [ 9 ]. Furthermore, high LET (Carbon ions) radiation induced more secretion of bystander factors in chondrocytes, compared to low LET (X-ray).…”

“…This is a huge advance for clinical cancer therapy considering the capacity of heavy charged particles in depositing most of their energy at tumour site and lower deposition in surrounding normal tissues. RT using low LET radiation, such as photon, induced cell death mostly by free radical production and water radiolysis while high LET radiation acts mostly by lethal damage in DNA, with a low possibility of DNA repair [ 9 ]. This damage was evidenced both in direct irradiated cells or tissues as well as in distant non-irradiated, for different types of radiation and tissues [ 10 ].…”