PHYSICAL CARCINOGENESIS

Physical Carcinogens What Are They and How Do They Act?

A carcinogen is anything that causes cancer in humans or animals. Carcinogens can be chemical or
physical agents or radiation. Chemical carcinogens include molecular substances that are found in a
variety of different compounds, such as cigarette smoke and some pesticides; physical carcinogens are
particles of soft or hard material that are not soluble in water. They exist as a solid compound.
Ionizing radiation is an example of a radioactive carcinogen, as is found in UV light and medical xrays.
The ability of carcinogens to produce cancer has been determined by observation of human cancer
development or by laboratory experiments in animals. Substances that produce cancer in humans are
referred to as known carcinogens. Many more substances fall into the category of possible
carcinogens. These substances may produce cancer in laboratory animals, or be loosely linked to
human cancers.
Physical carcinogens include fibers, particulate matter, hard and soft synthetic materials and gels.
Some physical carcinogens are naturally occurring, while others are synthetic. Physical carcinogens
are highly variable in their chemical structure, and many of them are poorly understood. Furthermore,
the method by which they cause cancer is even more mysterious. No specific pathway has been
isolated that correctly identifies the way physical agents cause cancer. Most likely, cancer can be
caused by a variety of different pathways. To complicate matters, some physical carcinogens act in
concert with genetic factors and other environmental agents to produce cancer. For instance, asbestos
can cause cancer on its own; however, it has much stronger carcinogenic potential when combined
with exposure to cigarette smoke.
Types of materials
Fibers
Physical carcinogens are highly variable in their structure. Fibers, such as asbestos, are some of the
more commonly recognized agents. These fibers may be naturally occurring and mined for public use,
or may be man made. Most fibers enter the body via inhalation, although they can also be swallowed,
or injected into the body in the laboratory setting. Fibers can be found in a variety of different shapes
and sizes. Humans are most commonly exposed to fiber carcinogens during work involving mining of
or construction with the material.
The most well-known physical carcinogen is asbestos. Asbestos is a silicate fiber that was for many
years,mined and used in insulation, furnaces, railways and automobile brakes. There are six forms of
asbestos fibers, with some possessing stronger carcinogenic activity than others. Asbestos usually
enters the body via inhalation, although it can theoretically be ingested or deposited in the skin. The
types of cancer most commonly linked to asbestos are mesothelioma and lung cancer.

Other fibers that are physical carcinogens include erionite and glass wool. Erionite is a naturally
occurring fiber made of zeolite with a crystalline structure; it is also associated with mesothelioma.
Glass wool is a manmade fiber that was used as a substitute for asbestos. After it was put into use,
experimental and epidemiological studies demonstrated its ability to produce lung cancer and
mesothelioma. Other natural fibers that are carcinogenic include wollastonite, attapulgite and
asbestiform fibers; manmade fibers that are physical carcinogens include rock wool, slag wool and
ceramic fibers. Of these fibers, most of the evidence of carcinogenesis comes from animal studies.
The National Institute of Occupational Safety and Health has developed a plan for research into
asbestos fibers and their effects on human health.
Particles
Particulate matter includes a variety of different compounds that are naturally present as tiny particles.
These particles are, in some cases, mined for human use. They include metals such as cobalt and
nickel and crystals such as silica. Like fibers, particulate matter is most often inhaled, but can also be
ingested into the digestive tract. Carcinogenic particulate matter includes metallic cobalt, nickel and
crystalline silica. When injected into the subcutaneous tissue, metallic cobalt and metallic nickel
produce sarcomas, a type of soft tissue tumor. Inhaled crystalline silica produced lung cancer, and can
produce lymphomas when injected into the chest or abdominal cavities of laboratory animals.
Hard and soft materials
This is a broad category that includes metallic alloys used in joint replacement surgery and synthetic
plastics used in vascular surgery. Most of the tumors observed with these materials have been
demonstrated in laboratory animal studies; the most common type of tumor seen is a sarcoma. While
cancer has been reported in a small number of human, the risk of cancer associated with surgical
implants is extremely low. Other materials associated with cancer include gold , platinum, silver,
steel and a variety of different plastics.
Silicon gel, used in breast implants , is another potential physical carcinogen. When injected into
animals, it produces fibrosarcomas and plasmacytomas. However, epidemiological studies of women
with silicone breast implants does not show any increased risk of malignancy in humans.
Methods of carcinogenesis
The biochemical mechanisms of cancer development associated with physical agents is uncertain, and
several different theories exist. One theory holds that the physical particles cause irritation in the
surrounding tissue, resulting in inflammation. The bodys normal inflammatory response involved
proliferation of surrounding cells and infiltration of the tissue with new cells. As the particle remains
in place and the normal tissue continues to undergo proliferation, some cells mutate into neoplastic
(cancer) cells. This idea is supported by studies showing particles of asbestos and erionite with larger
surface area to have a higher risk of cancer; the larger surface area is thought to allow more cells to
come into contact with the particle, leading to more inflammation. In animal experiments, prolonged
exposure to airborne particles results in accumulation of the particles within the lungs. This
theoretically results in chronic inflammation and increased risk of cellular mutation.
Another theory is based on the fact that some physical materials undergo deterioration over time. This
suggests that there is some sort of chemical reaction between the physical agent and the surrounding
tissue. This chemical reaction may have carcinogenic effects on the cells in the vicinity, allowing
them to become neoplastic.

On a molecular levels, the chemical reactions of some carcinogens are known, although incompletely.
Ultimately, carcinogens result in damage to DNA within cells. This damage has a number of effects,
including prolonged growth and spread of cancer cells throughout the body. One way that DNA can
be damaged is by reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS
are produced by certain chemical reactions, and are capable of physically damaging DNA. A number
of studies have shown physical carcinogens, including fibers such as asbestos and metals such as
nickel and copper, to produce ROS and RNS within cells.
Some metals, such as nickel and arsenic, are such small particles that they can travel inside cells and
directly damage DNA. They can due this by altering the structure or interfering with normal function
of the DNA.
Another possible way for physical material to cause cancer is by electrical forces. Surgically
implanted metals, such as those used in joint replacement, are very rarely associated with cancer.
These cancers may occur due to electrical forces on the surface of the metals causing DNA damage to
surrounding tissue.
Implantable devices may also increase the risk of cancer if they are associated with longstanding
infection. Because infection is associated with inflammation, a long-lasting infection may result in
cellular proliferation and mutation into cancer.
Conclusion
Many different agents can act as physical carcinogens. Some, such as asbestos, were widespread and
are linked to thousands of human cancers. In Eastern Europe, erionite is still prevalent. Other agents,
such as metallic or silicone implants, are only loosely linked to human cancers and the risk of cancer
development is extremely low or absent.
The method by which physical agents cause cancer is incompletely understood. Inflammation
surrounding the foreign body may play a role. Additionally, minute particles of the material may be
able to interact directly with cells of the body and damage the genetic material, leading to mutated
cells that eventually become cancer.
Physical agents are much more likely to cause cancer in animal models than in humans; the reason for
this difference is unknown. For example, silicone implants cause cancer in a number of experimental
animal studies, but no such link has been identified in humans.
The International Agency for Research on Cancer (IARC) regularly provides updated lists of known
and suspected carcinogens. Laboratory research is continually performed in an effort to identify
carcinogens and prevent human exposure.