Mutagens are chemicals or physical factors (such as radiation) that increase the rate of mutation in the cells of bacteria, plants, and animals (including humans). Most mutagens are of natural origin and are not just a modern phenomenon: even dinosaurs were susceptible to mutagens. Mutagens can be found in the food we eat, the air we breath, or the ground we walk on. Very small doses of a mutagen usually have little effect while large doses of a mutagen could be lethal.DNA in the nuclei of all cells encodes proteins that play important structural and functional (metabolic) roles in the cell. Mutagens typically disrupt the DNA of cells, causing changes in the proteins that the cell produces which can lead to abnormally fast growth (cancer), or even cell death. In rarer incidences mutagens can even cause protein changes that are beneficial to the cell.
The first mutagens to be identified were carcinogens, or cancer-causing substances. Early physicians detected tumors in patients more than 2,000 years before the discovery of chromosomes and DNA. In 500 b.c., the Greek Hippocrates named crab-shaped tumors cancer (meaning crab).
In England in 1775, Dr. Percivall Pott wrote a paper on the high incidence of scrotal cancer in chimney sweeps who were typically boys small enough to fit inside chimneys and clean out the soot. Pott suggested that chimney soot contained carcinogens that could cause the growth of the warts seen in scrotal cancer. Over a 150 years later, chimney soot was found to contain hydrocarbons capable of mutating DNA.
In France in the 1890s, Bordeaux wine workers showed an unusually high incidence of skin cancer on the back of the neck. These workers spend their days bending over in the fields picking grapes, so exposing the back of their necks to the sun. The ultraviolet (uv) radiation in natural sunlight was later identified as a mutagen.
Mutagens can be found in foods, beverages, and drugs. Sometimes a substance is mutagenic because it is converted in the body into something harmful. Regulatory agencies are responsible for testing food and drugs to insure that the public is not unknowingly exposed to mutagens. However, some mutagen-containing substances are not tightly controlled. One such substance is found in the tobacco of cigars and cigarettes.
Some mutagens occur naturally, and some are synthetic. Cosmic rays from space are natural, but they are mutagenic. Some naturally occurring viruses are considered mutagenic since they can insert themselves into host DNA.Hydrogen and atomic bombs are manmade, and they emit harmful radiation. Radiation from nuclear bombs and gaseous particles from nitrogen mustard and acridine orange have been used destructively in war. On the other hand, some mutagens are used constructively to kill bacteria that could grow in human foods, such as the small doses of nitrites used to preserve some meat. Even though nitrites can be mutagenic, without the nitrites these meats could cause botulism; hence, the benefit outweighs the risk involved.
Mutagens affect DNA in different ways. Some mutagens such as nitrogen mustard bind to a base and cause it to make a different amino acid. These mutagens cause point mutations, because they change the genetic code at one point, so changing a protein's amino acid sequence.
Mutagens such as acridine orange work by deleting or inserting one or more bases into the DNA molecule, so shifting the frame of the triplet code for an amino acid. Deletion and insertion mutations causing "frame-shift" mutations can change a long string of amino acids, which can severely alter the structure and function of a protein product.
Normal cells recognize cues from their environment and respond with specific reactions, but cells impaired by a mutation do not behave or appear normal, and are said to be transformed.
Mutations in somatic (body) cells are not transferred to offspring. Mutated DNA can only be passed to the next generation if it is present in a germ cell such as spermatozoa and ova (eggs), each of which contribute half of the DNA of the new organism.
Chemical mutagens are classified as alkylating agents, cross-linking agents, and polycyclic aromatic hydrocarbons (PAHs). Alkylating agents act by adding molecular components to DNA bases, so altering the protein product. Cross-linking agents create covalent bonds with DNA bases, while PAHs are metabolized by the human body into other potentially mutagenic molecules.
Radiation is a potent mutagen, classified as UV or ionizing radiation. UV radiation causes covalent bonds to form between neighboring thymine bases in the DNA, so altering the DNA product at that location. Ionizing radiation includes the x rays, gamma rays, and subatomic particles. Ionizing radiation alters the way two strands of DNA interact. This high energy radiation passes through cells and tissues, cutting up any DNA in its path. Ionizing radiation can rearrange entire sections of the chromosomes, altering relatively long stretches of DNA.
Mutagens are often associated with specific cancers in humans. Aromatic amines are mutagens that can cause bladder cancer. Tobacco taken in the form of snuff contains mutagens that can cause nose tumors. Tobacco smoke contains mutagens such as PAHs and nitrosamine (a type of alkylating agent), as well as toxins such as carbon monoxide, cyanide, ammonia, arsenic, and radioactive polonium. Although tobacco products are legally and widely available, many physicians and government agencies warn about the health risks linking smoking with several types of cancer and heart disease.
In 1973, Bruce Ames introduced the most widely-used test to identify potential mutagens. Suspected mutagens are mixed with a defective strain of the bacteriaSalmonella, which only grows if it is mutated. Substances which allow the Salmonella to grow are considered mutagenic.
In addition to mutagen-induced DNA changes, spontaneous mutations occur in the dividing cells of the human body every day. The nuclei of the cells have repair enzymes that remove mutations and restore mutated DNA to its original form.
If these natural DNA repair mechanisms fail to keep up with the rate of mutation or the repair mechanisms themselves are defective, then disease can result. This latter case is seen in lung cancer due to cigarette smoking, where the nicotine in the smoke is thought to block an important repair process in the lungs.
This is the complete article, containing 1,009 words
(approx. 3 pages at 300 words per page).
