Mutagen

In genetics, a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are typically also carcinogens. Not all mutations are caused by mutagens: so-called "spontaneous mutations" occur due to errors in DNA replication, repair and recombination.

Effects of mutations

The changes in nucleic acid sequences by mutations include substitution of nucleotide base-pairs and insertions and deletions of one or more nucleotides in DNA sequences. Although some of these mutations are lethal, or cause serious disease, many have minor effects, as the changes they cause in the sequence of encoded proteins are not significant. Many mutations cause no visible effects at all, either because they occur in introns or because they do not change the amino-acid sequence, due to redundancy of codons. On rare occasions they can create beneficial mutations, such as disease resistance, and can spur evolutionary change in a population.

Genetic drift

The change in a population’s genetic material due to the accumulation of random chance mutations is called genetic drift, and serves as a molecular clock. In general, the more nucleotide differences between two organisms, the more time has elapsed since their last common ancestor. Though it is difficult to determine in many organisms, estimates for mutation rates have been made for both E. coli and eukaryotes. It was estimated that, in these organisms, about one nucleotide in every 10¹⁰ is changed, and continues through reproduction to future generations of cells.

Discovery of mutagenesis

In the 1920s, Hermann Muller discovered that x-rays caused mutations in fruit flies. He went on to use x-rays to create Drosophila mutants that he used in his studies of genetics. He also discovered that x-rays not only mutate genes in fruit flies but also have effects on the genetic makeup of humans. 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 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, exposing the back of their necks to the sun. The ultraviolet (UV) radiation in natural sunlight was later identified as a mutagen.

Nature of mutagens

Mutagens are usually chemical compounds or ionizing radiation. Mutagens can be divided into different categories according to their effect on DNA replication:

• Some mutagens act as base analogs and get inserted into the DNA strand during replication in place of the substrates.
• Some react with DNA and cause structural changes that lead to miscopying of the template strand when the DNA is replicated.
• Some work indirectly by causing the cells to synthesize chemicals that have the direct mutagenic effect.

The Ames test is one method to determine how mutagenic an agent is.

Examples

• Ionizing radiation, for example X-rays, gamma rays and alpha particles
• Ultraviolet, electromagnetic radiation with a wavelength shorter than that of visible light but longer than x-rays
• Base analog, which can substitute for DNA bases and cause copying errors
• Deaminating agents such as nitrous acid
• Intercalating agents such as ethidium bromide
• Alkylating agents such as ethylnitrosourea
• Transposon, a section of DNA that undergoes autonomous fragment relocation/multiplication
• Alkaloid plants, such as those from Vinca species[citation needed]
• Bromine and some compounds that contain bromine in their chemical structure
• Sodium azide, an azide salt that is a common reagent in organic synthesis and a component in many car airbag systems
• Psoralen combined with ultraviolet radiation causes DNA cross-linking and hence chromosome breakage
• Benzene, an industrial solvent and precursor in the production of drugs, plastics, synthetic rubber and dyes
• Radioactive decay, such as ¹⁴C in DNA

Mutagens in action

The inhalation of aniline vapor may, after a latent period of many years, cause benign and malignant tumors of the bladder. On the foundation of the arsenic eczema of vineyard workers (caused by sprays against vineyard pests) carcinomas develop on the palms and soles. Chromate and asbestos dusts have been blamed for the development of lung cancer.

Mutagens in fiction

In science fiction, mutagens are often represented as substances that are capable of completely changing the form of the recipient. This is seen in the Teenage Mutant Ninja Turtle franchise, comic books such as Marvel Comics's Inhumans, television series, computer and video games, like the Metroid Prime Trilogy, Resistance: Fall of Man, Resident Evil, Infamous, and Command & Conquer, and even toys. For more examples, see List of mutagens in fiction.

See also

• Carcinogen
• DNA repair
• Genetics
• Genotoxicity
• Pesticide
• Teratogen