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 x-rays.
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
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.
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 body’s 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.
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.