Radiotherapy and Its Side Effects: Chapter 2 - Side Effects of Radiotherapy

PART II

Chapter 2

Side Effects of Radiotherapy (Cont'd)

Additional information about the side effects of radiotherapy

Because a human body is a delicate and complicated biological system, and the inter-communication among different organs are even more complex, some side effects are inter-connected and may not be clearly separated from one another. Let’s use some examples for further illustration.

Cancer patients treated by high dose radiation onto specific organ may suffer organ damages in addition to other side effects (hair loss, diarrhea, etc.). Let’s look at the radiotherapy on liver cancer as a specific example. Patients with liver cancer, when treated by ionizing radiation, may suffer from liver damage and/or liver function reduction.

There are several reasons why organ damages occur after radiation therapy. The obvious reason is that liver cells damaged by DNA will result in the damage of liver tissue through mechanisms such as programmed cell death (apoptosis). The other important reason is that certain cytokines, such as TNF-a, in liver and blood are often markedly induced by radiation therapy. As described before, abnormally elevated levels of TNF-a will kill the surrounding cells (no matter cancer cells or normal cells), and will cause certain liver damage. 

Our experimental results showed that radiation in mouse liver induced liver damage (reflected by elevated serum levels of both aspartate transaminase (AST) and alanine transaminase (ALT), and the liver damage is in correlation with increased levels for serum TNF-a induced by irradiation. Pre-treatment of mice with a small-molecule TNF-a modulator UTL-5d (Fig. 2.2) effectively reduced TNF-a secretion and resulted in marked reduction of ALT/AST levels. This implies that TNF-a may play an important role in damaging the liver and UTL-5d compound may be a potential agent for radioprotection.

                                                                    Fig. 2.2   Structure of UTL-5d

    In order to reduce the side effects induced by radiotherapy, there are several general strategies being employed as described in the next chapter. 

© Jiajiu Shaw, 2021

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Radiotherapy and Its Side Effects: Chapter 2 - Side Effects of Radiotherapy

PART II

Chapter 2

Side Effects of Radiotherapy (Cont'd)

3. Activation of immunologic responses

    In addition to producing the direct DNA damage, radiation can also produce a lot of free radicals, including reactive oxygen species (ROS), and cause indirect damages to normal tissues/organs.  The delicate immune system can also be disturbed by this oxidative stress, causing extraordinary number of immunological responses, including the abnormal release of many cytokines.

    Cytokines are regulatory proteins released by cells of the immune system. It has been reported that a number of cytokines may be induced by radiation, including tumor necrosis factor alpha (TNF-α), IL-1, IL-4, IL-5, IL-6, IL-8, IL-10, and transforming growth factor beta (TGF-β).  The alteration of cytokine levels in blood, skin, or other tissues can cause a number of pharmacological responses. 

© Jiajiu Shaw, 2021

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Radiotherapy and Its Side Effects: Chapter 1 - Introduction

PART II

Chapter 1

Introduction (cont'd)

Indeed, most of the therapeutic effect (DNA damage in the fast-growing cancer cells) by radiation is resulted from the DNA damage in cancer cells. Unfortunately, some normal cells can also be damaged by radiation because they are also fast-growing. These fast growing normal cells include bone marrow cells, hair follicle cells,  intestinal cells, and mucosal cells.

 Fortunately, there is a very important cellular function, DNA repair, by which a cell identifies and corrects damage to the DNA molecules. In fact, DNA repair process is constantly active as it responds to the continued damage in the DNA structure.

 Because cancer cells are not completely differentiated, their DNA repair capabilities tend to be less complete than those of normal cells. Therefore, cancer cells tend to be more susceptible to radiation damage as compared to normal cells. On the other hand, cancer cells can still rely on residual DNA repair capabilities to survive damage induced by radiotherapy or chemotherapy; this is one of the reasons cancer is not easy to treat.

In addition to radiation-induced DNA damage to normal cells, there are additional undesirable biological effects on the body, including immunological responses (such as abnormal levels of some cytokines including TNF-a, TGF-β, IL-12, and PGE2). These side effects will be discussed in the later section.

Indeed, the goal of radiotherapy is to damage as many cancer cells as possible, while limiting the damage to nearby healthy tissues/organs as much as possible. Nevertheless, it is almost impossible to have zero damage on normal cells. That is why the treatment plan is to focus the radiation to tumor cells. Let’s take a closer look at the side effects induced by radiotherapy in the following chapter.

© Jiajiu Shaw, 2020

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

What Can One Do to Reduce the Chances of Getting Cancer (4)

Innate Immune system

The innate immune system is evolutionally older; it is the dominant but non-specific protective system in human being.  It has several components including (1) the skin and surface barriers, (2) inflammation, (3) complement system, and (4) others.

The outermost layer of our skin comprises primarily one type of protective cells, keratinocytes, which serve as a general barrier to protect us against outside invaders, including bacteria, viruses, UV light, etc.  If the outside invader breaks into the skin (e.g., through a cut), keratinocytes can also produce proinflammatory biomolecules, such as TNF-α, as an additional layer of protection.  In one of our studies, we showed that UV light elevated levels of TNF-α released from an artificial skin and one of our compounds, UTL-5d, lowered TNF-α levels, indicating that it may be a potential ant-inflammatory agent.  Generally, elevated TNF-α levels indicate that inflammation is on its way. 

Other surface barriers in the body include the lungs and the GI tract; each has its own way to protect the body from outside invaders.  One specific example is mucus, which works to trap and expel outside invaders.

Another component of the innate immune system is complement system, which assist antibodies and phagocytic cells to clear pathogens.  The complement system comprises a number of proteins in blood.  When stimulated by outside invaders, specific protein(s) will be cleaved to release cytokines and initiate further immune responses to protect the body.

 Assuming a human body is a nation, the innate immune system is similar to a more rigid pre-structured national defense system, air force, army, navy, and marine.  In addition, the innate immune system can also recruit immune cells to sites of infection, through the production of special chemicals, such as cytokines.  It can also activate the complement cascade to identify bacteria, and remove foreign substances by white blood cells.

Furthermore, the innate immune system can also activate the adaptive immune system by antigen presentation.  This is very similar to a real life situation wherein a special situation in a foreign country requires Department of Defense (Innate immune system) to organize a special force (adaptive immune system) to counter and resolve the situation.

Note: 

What are Cytokines?

Cytokines are signaling proteins for cell to cell communication and interactions.  They are important regulators of both the innate and adaptive immune systems.  Examples of cytokines include interleukins (IL), interferons, and tumor necrosis factors (TNF).  Cytokines are different from hormones in that almost all cells are capable of producing cytokines whereas hormones are secreted by discrete glands.

© Jiajiu Shaw, 2017

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book I wrote, "IS CANCER IN US", published recently.