Carcinogen

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Ultraviolet (UV) irradiation from sunlight is a known human carcinogen. Ultraviolet photons harm the DNA molecules of living organisms in different ways. In one common damage event, adjacent Thymine bases bond with each other, instead of across the "ladder." This makes a bulge, and the distorted DNA molecule does not function properly.

A carcinogen is any substance or agent that can cause cancer. A carcinogen can be a chemical, radiation, radionuclide (an atom with an unstable nucleus), virus, hormone, or other agent that is directly involved in the promotion of cancer or in the facilitation of its propagation. This may be due to genomic instability or to the disruption of cellular metabolic processes. The process of induction of cancer is called carcinogenesis (Bender and Bender 2005).

Common examples of carcinogens are tobacco smoke, inhaled asbestos, benzene, hepatitis B, and human papilloma virus. Ultraviolet light from the sun is tied to skin cancer. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays or alpha particles, that they emit.

Contents

The human body is a masterpiece of harmoniously interrelated cells, tissues, organs, and systems, all working together in coordination. Cancer represents a severing of this intricate coordination. Reducing exposure to carcinogens touches upon personal and social responsibility. There is a personal responsibility not to expose oneself unnecessarily to known carcinogenic agents, such as smoking tobacco. There also is a responsibility on behalf of society to identify cancer-causing agents, doing assessments for them, implementing laws to remove potential carcinogens, and providing educational programs to warn the public, despite the high costs of such efforts.

Overview: Cancer, carcinogens, and DNA

Cancer is a disease characterized by a population of cells that grow and divide without respect to normal limits, invade and destroy adjacent tissues, and may spread to distant anatomic sites through a process called metastasis. These malignant properties of cancers differentiate them from benign tumors, which are self-limited in their growth and do not invade or metastasize (although some benign tumor types are capable of becoming malignant).

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth.

Carcinogens may increase the risk of getting cancer by altering cellular metabolism or damaging DNA directly in cells, which interferes with biological processes, and induces the uncontrolled, malignant division ultimately. Usually DNA damage, if too severe to repair, leads to programmed cell death, but if the programmed cell death pathway is damaged, then the cell cannot prevent itself from becoming a cancer cell.

Genetic abnormalities found in cancer typically affect two general classes of genes: Oncogenes and tumor suppressor genes. When these genes are mutated by carcinogens they contribute to malignant tumor formation (Narins 2005).

Oncogenes ("onco-" means tumor) are altered versions of normal genes, called proto-oncogenes, that encode proteins that are involved in such functions as regulating normal cell growth and division (Narins 2005). When the proto-oncogene is mutated to an oncogene by exposure to a carcinogen, the resultant protein may lack ability to govern cell growth and division, resulting in unrestrained and rapid cell proliferation (Narins 2005). In addition to hyperactive growth and division, cancer-promoting oncogenes may be activated which give cells such new properties as protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Numerous cancers are associated with mutation in one particular proto-oncogene, ras, which codes a protein that acts to regulate cell growth (Narins 2005).

Tumor suppressor genes encode proteins that commonly tend to repress cancer formation. When they are inactivated by carcinogens, this results in loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Classification of carcinogens

Carcinogens can be classified as genotoxic or nongenotoxic.

Genotoxic means the carcinogens interact physically with the DNA to damage or change its structure (Breslow 2002). Genotoxins cause irreversible genetic damage or mutations by binding to the DNA. Genotoxins include chemical agents like N-Nitroso-N-Methylurea (MNU) or non-chemical agents such as ultraviolet light and ionizing radiation. Certain viruses can also act as carcinogens by interacting with DNA.

Nongenotoxic are carcinogens that change how DNA expresses its information without changes in the DNA strucutre directly, or may create a situation whereby the cell or tissue is more susceptible to DNA damage from another source. Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds (Longe 2005). Examples of nongeotoxic carcinogens or promoters are arsenic and estrogen (Breslow 2002).

Some carcinogens also may interfere with cell division, by changing the structure or number of chromosomes in new cells after cell division (Breslow 2002). An example of this is nickel.

IARC classification of carcinogens

The following is the classification of carcinogens according to the International Agency for Research on Cancer (IARC):

  • Group 1: The agent (mixture) is definitely carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
  • Group 2A: The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
  • Group 2B: The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
  • Group 3: The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
  • Group 4: The agent (mixture) is probably not carcinogenic to humans.

Further details can be found in the IARC Monographs.

Examples of carcinogens

Carcinogens essentially produce cancer by changing the information cells receive from their DNA, resulting in accumulation of immature cells in the body, rather than the cells differentiating into normal, functioning cells.

There are many natural carcinogens. Aflatoxin B1, which is produced by the fungus Aspergillus flavus growing on stored grains, nuts, and peanut butter, is an example of a potent, naturally-occurring microbial carcinogen. Certain viruses such as hepatitis B and human papilloma viruses have been found to cause cancer in humans. The first one shown to cause cancer in animals was Rous sarcoma virus, discovered in 1910 by Peyton Rous.

Benzene, kepone, EDB, asbestos, and the waste rock of oil shale mining have all been classified as carcinogenic. As far back as the 1930s, industrial and tobacco smoke were identified as sources of dozens of carcinogens, including benzopyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde—which is also a hazard in embalming and making plastics. Vinyl chloride, from which PVC is manufactured, is a carcinogen and thus a hazard in PVC production.

DNA is nucleophilic, therefore, soluble carbon electrophiles are carcinogenic, because DNA attacks them. For example, some alkenes are toxicated by human enzymes to produce an electrophilic epoxide. DNA attacks the epoxide, and is bound permanently to it. This is the mechanism behind the carcinogenity of benzopyrene in tobacco smoke, other aromatics, aflatoxin, and mustard gas.

After the carcinogen enters the body, the body makes an attempt to eliminate it through a process called biotransformation. The purpose of these reactions is to make the carcinogen more water-soluble so that it can be removed from the body. But these reactions can also convert a less toxic carcinogen into a more toxic one.

Co-carcinogens are chemicals which do not separately cause cancer, but do so in specific combinations.

Radiation

CERCLA (Comprehensive Environmental Response, Compensation, and Liability Act, the environmental law enacted by the United States Congress in 1980) identifies all radionuclides as carcinogens, although the nature of the emitted radiation (alpha, beta, or gamma, and the energy), its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. For example, Thorotrast, a (incidentally-radioactive) suspension previously used as a contrast medium in x-ray diagnostics, is thought by some to be the most potent human carcinogen known because of its retention within various organs and persistent emission of alpha particles. Both Wilhelm Röntgen and Marie Curie died of cancer caused by radiation exposure during their experiments.

Not all types of electromagnetic radiation are carcinogenic. Low-energy waves on the electromagnetic spectrum are generally not, including radio waves, microwave radiation, infrared radiation, and visible light. Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, generally is carcinogenic, if received in sufficient doses.

Carcinogens in prepared food

Cooking food at high temperatures, for example broiling or barbecuing meats, can lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzopyrene) (Zheng et al. 1998). Charring of food resembles coking and tobacco pyrolysis and produces similar carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human enzymes into epoxides, which attach permanently to DNA. Pre-cooking meats in a microwave oven for 2-3 minutes before broiling shortens the time on the hot pan, which can help minimize the formation of these carcinogens.

Recent reports have found that the known animal carcinogen acrylamide is generated in fried or overheated carbohydrate foods (such as french fries and potato chips). Studies are underway at the U.S. Food and Drug Administration (FDA) and European regulatory agencies to assess its potential risk to humans. The charred residue on barbecued meats has been identified as a carcinogen, along with many other tars.

Nevertheless, the fact that the food contains minute quantities does not necessarily mean that there is a significant hazard. The gastrointestinal tract sheds its outer layer continuously to protect itself from carcinomas, and has a high activity of detoxifying enzymes. The lungs are not protected in this manner, therefore smoking is much more hazardous.

Saccharin, a popular calorie-free sweetener was found to be a carcinogen in rats, resulting in bladder cancer (Breslow 2002). However, being carcinogenic in laboratory animals does not necessarily translate to being carcinogens in people because of differences in how substances are metabolized and how they produce cancer (Breslow 2002).


References

  • Bender, D. A., and A. E. Bender. 2005. A Dictionary of Food and Nutrition. New York: Oxford University Press. ISBN 0198609612
  • Breslow, L. 2002. Encyclopedia of Public Health. New York: Macmillan Reference USA/Gale Group Thomson Learning. ISBN 0028658884
  • Longe, J. L. 2006. The Gale Encyclopedia of Medicine. Detroit: Thomson Gale. ISBN 1414403682
  • Longe, J. L. 2005. The Gale Encyclopedia of Cancer: A Guide to Cancer and Its Treatments. Detroit: Thomson/Gale. ISBN 1414403623
  • Narins, B. 2005. The Gale Encyclopedia of Genetic Disorders. Detroit, Mich: Thomson/Gale. ISBN 1414404735
  • Zheng, W., D. R. Gustafson, R. Sinha, J. R. Cerhan, et al. 1998. Well-done meat intake and the risk of breast cancer. Journal of the National Cancer Institute 90(22): 1724.

External links

All links retrieved April 8, 2013.

Tumors (and related structures), Cancer, and Oncology
Benign - Premalignant - Carcinoma in situ - Malignant

Topography: Anus - Bladder - Bone - Brain - Breast - Cervix - Colon/rectum - Duodenum - Endometrium - Esophagus - Eye - Gallbladder - Head/Neck - Liver - Larynx - Lung - Mouth - Pancreas - Penis - Prostate - Kidney - Ovaries - Skin - Stomach - Testicles - Thyroid

Morphology: Papilloma/carcinoma - Adenoma/adenocarcinoma - Soft tissue sarcoma - Melanoma - Fibroma/fibrosarcoma - Lipoma/liposarcoma - Leiomyoma/leiomyosarcoma - Rhabdomyoma/rhabdomyosarcoma - Mesothelioma - Angioma/angiosarcoma - Osteoma/osteosarcoma - Chondroma/chondrosarcoma - Glioma - Lymphoma/leukemia

Treatment: Chemotherapy - Radiation therapy - Immunotherapy - Experimental cancer treatment

Related structures: Cyst - Dysplasia - Hamartoma - Neoplasia - Nodule - Polyp - Pseudocyst

Misc: Tumor suppressor genes/oncogenes - Staging/grading - Carcinogenesis/metastasis - Carcinogen - Research - Paraneoplastic phenomenon - ICD-O - List of oncology-related terms


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