Carcinogens
Carcinogens are substances that can cause cancer by altering the DNA within cells, leading to uncontrolled cell growth. The classification of a substance as a "known" human carcinogen relies on evidence that establishes a causal relationship between exposure and cancer development, as recognized by agencies like the U.S. National Toxicology Program (NTP). The process of cancer development is complex, often occurring in stages, and can involve genetic mutations that may be inherited. Research indicates that various factors, such as genetics and lifestyle choices, contribute to an individual's cancer risk.
Testing for carcinogenic properties typically involves animal studies, focusing on substances that can cause mutations, as most carcinogens also act as mutagens. However, advancements have allowed for more efficient testing methods, including the use of bacteria and enzymes to identify potential carcinogens. While concerns about carcinogenic chemicals are prevalent, extensive research has shown that not all suspected chemicals are harmful; in fact, a significant portion of human cancers is linked to naturally occurring carcinogens. Understanding the types and mechanisms of carcinogens helps in assessing risks and guiding regulatory measures.
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Carcinogens
DEFINITION: A carcinogen is any substance that causes cancer. Generally, cancer occurs when a cell's DNA, i.e., its "genetic blueprint," has been changed. A “known” human carcinogen is a chemical compound identified by the National Toxicology Program of the U.S. Department of Health and Human Services as displaying “sufficient evidence of carcinogenicity in humans [to indicate] a causal relationship between exposure to the agent, substance, or mixture and human cancer.”
Chemicals and cancer: Certain chemicals are capable of causing cells in an organ of the body to grow uncontrollably. Scientists knew of malignant growths produced by exposure to particular chemicals as early as a century ago. The National Toxicology Program (NTP) produces a biennial Report on Carcinogens (RoC), which deals with carcinogenic compounds in humans, potential human exposure to these substances, and federal regulations of exposure limits to the chemicals. The introduction to the report defines a known carcinogen as a chemical for which there is sufficient evidence indicating a causal relationship between exposure and human cancer.
Definitive data on carcinogenicity are challenging to obtain because multiple exposures to the substance and a long induction period are often needed before a tumor appears. Genetics, lifestyle, and ethnic factors are important in developing certain tumors. The National Toxicology Program employs a variety of approaches but considers two-year studies in rodents to be its primary method of determining what substances are carcinogens.
Development of cancer: Cancers seem to develop in stages, showing substantial overlap and not progressing uniformly. Much research on the initiation stage has been devoted to the study of changes in deoxyribonucleic acid (DNA). Many carcinogenic chemicals have been shown to cause mutations. Bonding to a strand of DNA produces a mutation that might be replicated before it can be repaired. Such an error might be passed along to future generations. Most such mutations do not affect the cell, but if a protein associated with growth is involved, it might create the potential for future rapid cell growth. It is also believed that reactions between potential carcinogens and DNA do not occur in a random process but rather in the production of genes.
The way in which the promotion stage of cancer development proceeds is still obscure, but the nature of promoting substances provides clues. These compounds are believed to stimulate the production of multiple benign tumors. Their effect is reversible; with their withdrawal, the tumor disappears. They are, however, not able to produce the cancer by themselves.
At some point in the progression stage, another genetic change occurs that results in a selective growth advantage for the mutant cell. There are several ways in which such an event might take place:
- Additional exposures to the original carcinogen
- Spontaneous mutation from replication enzymes
- Changes in the genes caused by initiating mutations
The result is an irreversible change in the cell.
The malignant conversion stage produces a distinct growth advantage for the affected cell. Rodent studies have evidence that genetics is an important factor in these late-stage changes and in the early development of cancer. Experiments reveal protein synthesis, amplification of gene creation, and further DNA reactions at this stage in the tumor cell.
Testing for carcinogens: To determine whether a substance is a carcinogen, scientists use animal testing and also test for mutagens, relying on the fact that nearly all carcinogenic molecules also produce mutations. However, there are significant problems involved. A direct effort along this line involves seeking a lethal mutation involving the X chromosome, which determines the sex of the offspring.
The realization that intermediate products from detoxification may be the cause of the initiation phase of cancer development has led to the development of tests involving bacteria and enzymes. These procedures greatly reduced cost (one-thousandth as much as mice) and time (two days compared with at least a year). It has become possible to test all new compounds for mutations and to conduct animal tests only on those showing positive results. The National Toxicology Program is actively using all these approaches.
Achieving a balance: Although carcinogenic chemicals are of concern, it is essential to recognize the actual risk. Extensive studies conducted by the National Toxicology Program and the International Agency for Research in Cancer (IARC) show that only one-third of suspected chemicals are actually carcinogenic. Approximately 96 percent of human cancer results from naturally occurring carcinogens.
Intense study of such carcinogenic compounds shows that 95 percent involve only three types of chemicals:
- Alkylating agents: Transfer small fragments (CH3) to DNA
- Arylkylating agents: Transfer aromatic rings (C6H5) to DNA
- Arylhydroxylamines: Transfer amines, containing NH2 to DNA.
A common aspect of these materials is their ability to produce structures deficient in electrons. Such structures react rapidly with nucleic acid's electron-rich oxygen, sulfur, and nitrogen atoms.
Bibliography
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