Most information about cutaneous carcinogenesis has been obtained from studies using laboratory animals, especially mice. After topical application of a carcinogen at regular intervals, the animals develop multiple squamous papillomas, most of which regress spontaneously. Some of the lesions develop the cytologic criteria of malignant cells, and these tumors may become locally invasive.
The multistage carcinogenesis model developed on mouse skin tumors has provided a useful tool for the study of carcinogenesis. Three stages of progression have been identified for chemical carcinogenesis: initiation, promotion, and carcinogenesis. During the initiation phase, the DNA configuration of the cells undergoes some basic changes. The process of initiation may remain unchanged for the life of the tissue, or it may progress to malignancy. The epidermal cells in psoriasis share many features with initiated cells. The initiated cells are usually terminally differentiated but may lose their pattern of differentiation and retain their ability to multiply. For the promoter to be effective and cause malignancies, the cell must have been initiated previously. Most promoters usually cause inflammation and hyperplasia, and their effects are reversible. Promoters can induce tumors only after initiation. Some initiators and promoters are listed in. RasHa and N-ras have been found to be possible initiation events in chemically induced epidermal cancers in mice. Promoter compounds have been noted to induce increased production of transforming growth factor alpha in mice. This has been postulated to provide an environment that allows clonal expansion of initiated cells. Progression to malignant transformation has been noted in initiated cells containing rasHa that were given the activated v-fos oncogene. Cells containing either oncogene alone did not progress to carcinoma, suggesting the need for multiple activational events before progression occurs. As further exciting details come to light it should be kept in mind that these studies were undertaken in special populations of mice, and application to humans should be undertaken with caution.
Tar, which contains polycyclic aromatic hydrocarbons, is an initiator, and it has been used for treating psoriasis. Nitrogen mustard is an accepted treatment for cutaneous T-cell lymphoma. Phorbol esters, which are found in croton oil, are known promoters. Anthralin, used in the treatment of psoriasis, and benzoyl peroxide, used in the treatment of acne, are also known promoters. Long-term use of these agents in humans has not been associated with an increased incidence of malignancy. No chemical carcinogen has been identified that gives rise to basal cell carcinoma or malignant melanoma in animals, but experiments with cutaneous chemical carcinogenesis in laboratory animals cannot be directly applied to humans.
The well-documented cases of scrotal carcinoma in chimney sweepers offer the classic example of chemical carcinogenesis in humans. Arsenic is recognized as a chemical carcinogen. Increased incidence of cancers is reported in localities where there is a high level of arsenic in the drinking water. Medical exposure to arsenic in the form of Fowler’s solution, Donovan’s solution, and Asiatic pills in the treatment of asthma, psoriasis, and syphilis predisposes to the development of arsenical keratosis, skin cancer, and possibly lung cancer.
There are many risk factors for cancer: age, family history, viruses and bacteria, lifestyle (behaviors), and contact with (touching, eating, drinking, or breathing) harmful substances. More than 100,000 chemicals are used by Americans, and about 1,000 new chemicals are introduced each year. These chemicals are found in everyday items, such as
foods, personal products, packaging, prescription drugs, and household and lawn care products. While some chemicals can be harmful, not all contact with chemicals is dangerous to your health.
What is a carcinogen?
Cancer is caused by changes in a cell’s DNA – its genetic “blueprint.” Some of these changes may be inherited from our parents. Others may be caused by outside exposures, which are often referred to as environmental factors. Environmental factors can include a wide range of exposures, such as:
- Lifestyle factors (nutrition, tobacco use, physical activity, etc.)
- Naturally occurring exposures (ultraviolet light, radon gas, infectious agents, etc.)
- Medical treatments (radiation and medicines including chemotherapy, hormone drugs, drugs that suppress the immune system, etc.)
- Workplace exposures
- Household exposures
Substances and exposures that can lead to cancer are called carcinogens. Some carcinogens do not affect DNA directly but lead to cancer in other ways. For example, they may cause cells to divide at a faster than normal rate, which could increase the chances that DNA changes will occur.
Getting cancer from a chemical depends on the following:
• The kind of chemical you were exposed to,
• How much of the chemical you were in contact with,
• How long the contact lasted,
• How often you were exposed,
• When you were exposed,
• How you were exposed, and
• Your general health.
Exposure to chemicals in the outdoors, at home, and at work may add to your chances of getting cancer. Certain chemicals, including benzene, beryllium, asbestos, vinyl chloride, and arsenic are known human carcinogens, meaning they have been found to cause cancer in humans.
Types of Cancers Associated with Various Occupations or Occupational Exposure
Chemical exposures in the workplace can happen at high levels and over long periods
of time. That is why some jobs require that employees wear protective clothing and equipment and/or respirators. Companies are supposed to notify their employees of a
potential danger to their health.
These Substances or Processes can cause Lung Cancer
- coke oven fumes
- chromium compounds
- coal gasification
- nickel refining
- foundry substances
Aluminum production, rubber industry, leather industry, 4-aminobiphenyl, benzidine
Nasal cavity and sinuses
Formaldehyde, isopropyl alcohol manufacture, mustard gas, nickel refining, leather dust, wood dust
Larynx – Asbestos, isopropyl alcohol, mustard gas
Pharynx – Formaldehyde, mustard gas
Lymphatic and hematopoietic – Benzene, ethylene oxide, herbicides, x-radiation system
Skin – Arsenic, coal tars, mineral oils, sunlight
Soft-tissue sarcoma – Chlorophenols, chloro-phenoxyl herbicides
Liver – Arsenic, vinyl chloride
Lip – Sunlight
The human body has defenses to guard against all sorts of harmful exposures, including those that may lead to cancer. When something enters your body, it often goes through a
a process that allows the body to more easily use or get rid of it. This process is called metabolism. Depending on how a chemical is processed, or metabolized, in your body, three types of carcinogens exist:
• Chemicals that can cause cancer (direct-acting carcinogens),
• Chemicals that do not cause cancer unless they are changed when they are metabolized (procarcinogens), and
• Chemicals that do not cause cancer by themselves but can act with another chemical to cause cancer (cocarcinogens).
How are Carcinogens Classified?
International Agency for Research on Cancer
The International Agency for Research on Cancer (IARC) is part of the World Health Organization (WHO). One of its major goals is to identify causes of cancer. The most widely used system for classifying carcinogens comes from the IARC. In the past 30 years, the IARC has evaluated the cancer-causing potential of more than 900 likely candidates, placing them into one of the following groups:
- Group 1: Carcinogenic to humans
- Group 2A: Probably carcinogenic to humans
- Group 2B: Possibly carcinogenic to humans
- Group 3: Unclassifiable as to carcinogenicity in humans
- Group 4: Probably not carcinogenic to humans
Perhaps not surprisingly, based on how hard it can be to test these candidate carcinogens, most are listed as being of probable, possible, or unknown risk. Only a little over 100 are classified as “carcinogenic to humans.”
National Toxicology Program
The National Toxicology Program (NTP) is formed from parts of several different US government agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA). The NTP updates its Report on Carcinogens (RoC) every few years.
The Report on Carcinogens identifies 2 groups of agents:
- “Known to be human carcinogens”
- “Reasonably anticipated to be human carcinogens”
The current version of the RoC lists about 250 substances and exposures. Unlike the IARC’s list, the RoC does not list substances that have been studied and found not to be carcinogens.
Environmental Protection Agency
The US Environmental Protection Agency (EPA) maintains the Integrated Risk Information System (IRIS), an electronic database that contains information on human health effects from exposure to certain substances in the environment. The EPA uses a rating system similar to that of IARC when describing the cancer-causing potential of a substance:
- Group A: Carcinogenic to humans
- Group B: Likely to be carcinogenic to humans
- Group C: Suggestive evidence of carcinogenic potential
- Group D: Inadequate information to assess carcinogenic potential
- Group E: Not likely to be carcinogenic to humans