Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

Abstract

Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation.

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

“…High doses of radiation (>10 Gy) can cause a rapid wave of EC apoptosis, whereas surviving cells develop a dysfunctional vascular phenotype (57). Long-term effects include microvessel collapse, thickening of the basement membrane, and persistence of an activated, procoagulant endothelial phenotype (15,29). As a consequence, the irradiated tissue is converted into a hypoxic proinflammatory environment causing further damage to other normal cells by inducing ischemia, necrosis, and fibrosis (15,74).…”

“…In general, the response of the vasculature to radiation is classified in acute and late effects, both of which contribute to the initiation, progression, and maintenance of tissue damage (15). High doses of radiation (>10 Gy) can cause a rapid wave of EC apoptosis, whereas surviving cells develop a dysfunctional vascular phenotype (57).…”

“…Among these populations, the nondividing cells, the microvascular endothelial compartment has clearly been shown to play a central role in radiation toxicity in healthy tissues (15,61).…”

Single cell ionization by a laser trap: a preliminary study in measuring radiation dose and charge in BT20 breast carcinoma cells

“…Medicinally, radiotherapy is used largely to eradicate cancerous tissue by killing cancer cells. This is achieved largely by damaging the DNA sequence of the cancer cell, which either directly kills the cell by eliminating its ability to function or inhibits the cell's production ability, that is, sterilization [2]. However, radiation also has the same effect on the healthy cells that surround the cancerous tumor.…”

“…This is termed radiation-induced tissue toxicity. Radiation-induced tissue toxicity can consist of acute effects, or the more detrimental, late effects, such as ischemia, necrosis, and tissue fibrosis [2,3]. Thus, it is important to the patient's recovery that the damage done to healthy cells be minimized.…”