Download The Chemical Effects of Chemotherapy and Radiation on the

The Chemical Effects of Chemotherapy and Radiation on the Human Body
According to the National Cancer Institute, some 10.5 Million Americans are living with cancer.
With over one million diagnosed each year, the sooner treatment begins the better a patient’s
chances are of a cure. However, sometimes a patient is forced to overcome not only cancer, but
the damage inflicted by the dangerous chemicals in the treatments used to fight the disease.
Caused by exposure to carcinogens, genetic defects, or viruses, cancer is uncontrolled cell
growth. Although the disease usually forms as a tumor, some types of cancer, such as
leukemia, do not and instead involve the blood and blood-forming organs, circulating through
other tissues where they grow. The transformation of a normal cell into a cancer cell can occur
when the genetic material (deoxyribonucleic acid or DNA) of a cell is changed or mutated. This
substance is in every cell and directs all of the cell’s activities. Most of the time when DNA
becomes damaged either the cell dies or is able to repair the DNA. However, in cancer cells the
damaged DNA is not repaired. Cancer cells differ from normal cells in that they continue to
grow and divide. Instead of dying they outlive normal cells and carry on to grow and make new
abnormal cells. With so many different types of cancers that progress at different rates, it is
important to receive a treatment that is aimed at that particular type of cancer.
Although those that receive chemotherapy and radiation therapy may remain cancer-free,
some patients continue to experience pain and cognitive impairment that may result from longterm side effects of treatment. Radiation therapy and chemotherapy generally attack healthy
tissues as well as tumors, causing these long-and short-term complications.
Many chemotherapy drugs work only on cells that are actively reproducing (not on cells in the
resting phase, G0), while some drugs specifically attack cells in a particular phase of the cell
cycle (the M or S phases, for example). Chemotherapy damages part of the control center
inside each cell that makes cells divide. Or it will interrupt the chemical processes involved in
cell division, ultimately killing the cell. When chemotherapy drugs attack reproducing cells, they
cannot tell the difference between reproducing cells of normal tissues (that are replacing wornout normal cells) and cancer cells. It eventually ends up affecting the healthy body tissues
where the cells are constantly growing and dividing. This can lead to direct or indirect changes
in the central nervous system, cranial nerves, or peripheral nerves.
There is not just one type of drug used in chemotherapy; in fact there are over fifty commonly
used chemotherapy drugs. They are divided into several different groups based on a number of
factors. This includes how they work, their chemical structure, and their relationship to another
drug [1]. Often times more than one drug is used in treatment. Knowing how the drug works
helps the Oncologist predict what mixture of drugs should be used and what side effects they
will have on the patient. Some commonly used chemotherapy drug groups include: alkylating
agents, antimetabolites, anti-tumor antibiotics, topoisomerase inhibitors, mitotic inhibitors,
and corticosteroids.
Alkylating agents work by directly damaging the DNA to stop reproduction of the cancer cell [1]
(examples of classes of alkylating agents: Ethylenimines [thiotepa, alteramine], alkyl sulfonates
[busulfan], nitrogen mustards [mechlorethamine, chlorambucil, ifosfamide, melphalan],
nitrosoureas [streptoxocin, carmustine, lomustine], and triazines [dacarbazine, temozolomide].
Antimetabolites damage cancer cells by interfering with DNA and RNA growth by substituting
for the normal building blocks of RNA and DNA[1] (examples of antimetabolites: 5-fluorouracil,
6-mercaptopurine, capecitabine, cladribine, clofarabine, cytarabine, floxuridine, fludarabine,
gemcitabine, hydroxyurea, methotrexate, pemetrexed, pentostain, and thioguanine). Antitumor antibiotics are anthracyclines, antibiotics that interfere with enzymes involved in DNA
replication [1] (examples of anthracylines: daunorubicin, soxorubicin, epirubicin, idarubicin).
Topoisomerase inhibitors interfere with topoisomerase enzymes which help separate the
strands of DNA so they can be copied [1]. There are type I and type II inhibitors (topoisomerases
I inhibitors: topotecan, irinotecan and topoisomerases II inhibitors: etoposide, teniposide,
mitoxantrone). Mitotic inhibitors stop mitosis or inhibit enzymes form making proteins needed
for the reproduction of cells [1] (examples of mitotic inhibitors: taxanes [paclitaxel, docetaxel],
epothilones [ixabepilone], vinca alkaloids [vinblastine, vinorelbine], and estramustine. Finally,
corticosteroids are used to kill cancer cells or slow their growth [1] (examples of corticosteroids:
prednisone, methylpronisolone, and dexamethasone).
Each drug has its own set of side effects ranging from a decrease in blood cell counts, hair loss,
nausea, vomiting, jaw pain, to allergic reactions, seizures, and liver and kidney damage.
Researchers at the University of Rochester Medical Center and Harvard Medical School have
linked the widely use chemotherapy drug 5-fluorouracil (5-FU) to a progressing collapse of
populations of stem cells and their progeny in the central nervous system. 5-FU causes healthy
brain cells to die off long after treatment has ended and could be on the underlying biological
causes of cognitive impairment that cancer patients experience, referred to as “chemo brain”[2].
Until recently, chemo brain was often dismissed as the byproduct of fatigue, depression, and
anxiety related to cancer diagnosis and treatment. Causing neurological side effects such as
short-term memory loss and in severe cases, seizures, vision loss, and dementia, chemo brain
affects cognitive function bother acutely and chronically. Scientists exposed both individual cell
population and mice to doses of 5-FU in amounts comparable to those used in cancer patients.
Moths after exposure, researcher discovered that a specific population of cells in the central
nervous system- oligodenrocyts- underwent such extensive damage that these cells had all but
disappeared in the mice. Oligodenrocyts are responsible for producing myelin which coat nerve
cells and enable the signals between cells to be transmitted quick and efficiently. Without
oligodenrocyt, myelin membranes cannot be renewed and eventually break down, causing a
disruption in the impulse transmission between nerve cells [2]. This leads to the cognitive
difficulties seen in many cancer patients.
Like chemotherapy, radiation therapy produces its share of damage and short- and long-term
side effects as well. Because cancer cells usually multiply faster than most other cells in the
body, tissue composed of these quickly-dividing cells can be shrunken by disabling its genetic
material. By doing this, ionizing radiation interferes with the cancerous tissue’s ability to grow.
The radiation reacts with water in the cells and this reaction damages the DNA or genetic
material in the cell that controls cell growth. Unfortunately, the radiation makes no distinction
between cancerous cells and the rapidly dividing body tissues. Radiotherapy sometimes even
gives patient new tumors years later.
For those receiving radiotherapy, fibrosis in the tissue surrounding the tumor is quickly
becoming one of the biggest problem in cancer patients. The dangers of fibrosis depend on
where it occurs. In the breast it can cause loss of mobility; in the lungs it can limit breathing and
the ability to cough up infectious material; in the kidneys it can restrict fluid flow and lead to
infection. Fibrosis is the result of an overproduction of extracellular matrix (ECM), the fibrous
network of molecules between cells that determines structure and regulates function of
tissues. In fibrosis, tissues gradually lose their elasticity as ECM fills up the space between cells.
Radiation-induced fibrosis is influenced by a number of factors such as age, nutritional status,
coexisting morbidity, surgery, and biological differences between patients. Radiotherapyrelated factors can also play a major role in determining the extent of fibrosis. A study
published in the Journal of Cancer Research and Therapeutics shows that superiority of
accelerated partial breast irradiation (APBI) delivered by 3D conformal radiotherapy over
conventional treatment in reducing radiation-induced fibrosis in the breast. This is important in
a breast-conserving treatment, which can result in a poor cosmetic outcome with
radiotherapy [3].
Another study shows how researchers have produced a drug based on bacterial flagellin that
could possibly prevent tissue damage during radiation therapy or even nuclear terrorism. By
helping cells resist apoptosis, or self-destruction, the drug protects healthy tissues from the
cell-damaging effects of radiation. Andrei Fudlov of Roswell Park Cancer Institute and his
colleagues purified a batch of flagellin and administered it to rhesus monkeys and mice fifteen
minutes to one hour before exposing the animals to full-body, lethal doses of radiation. The
drug not only protected the animal’s cells but also toughened them against the effect of free
radicals (molecules that can damage DNA or genetic material inside them). Researchers then
produced a drug call CBLB502 that was designed to mimic flagellin; it protected eighty seven
percent of the animals form the lethal doses and also safeguarded against free-radical damage.
However, the drug did not appear to protect malignant cells from the radiation treatments
designed to kill them [4].
If proved safe in further testing the drug could be used to protect patients undergoing bone
marrow transplants or cancer treatments involving radiation. It could also be used in the event
of a nuclear explosion or meltdown [4].
The two most commonly used treatments in the fight against cancer- chemotherapy and
radiation therapy- can lead to such debilitating side effects that a patient often feels as if they
are fighting two different diseases. Although it is difficult for doctors to sometimes recognize
and untangle the many symptoms over the long course of a patient’s treatment, new research
has many hopeful about not only the relief of side effects caused by treatment but also the
possibility of making cancer therapy more effective.
Citations
[1]
"Different Types of Chemotherapy Drugs." Different Types of Chemotherapy Drugs. American
Cancer Society, Inc, 2013. Web. 19 Oct. 2013.
[2]
Meyers, Christina A. "How Chemotherapy Damages the Central Nervous System." Journal of
Biology 7.4: 11. Print.
[3]
Bahl, Amit, V. Subramani, Dn Sharma, Gk Rath, Pk Julka, and Ks Jothy Basu. "Normal Tissue
Complication Probability of Fibrosis in Radiotherapy of Breast Cancer: Accelerated Partial Breast
Irradiation vs Conventional External-beam Radiotherapy." Journal of Cancer Research and
Therapeutics 4.3 (2011): 126. Print.
[4]
Bhattacharjee, Y. "MEDICINE: Drug Bestows Radiation Resistance on Mice and Monkeys."
Science 320.5873 (2008): 163. Print.