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Understanding Mutagens responsible for Mutation
#1
Background: Mutagens cause changes (mutations) in the genetic material of cells. A mutation can be the result of different events. Errors made during replication, repair, or recombination can all lead to point or frameshift mutations. Mutations resulting from such errors are spontaneous mutations. A mutation can also result from the action of physical and chemical agents known as mutagens.


Gene, the basic unit of a DNA acts as genetic messenger. Genes are responsible for synthesis of proteins, the important biomolecule responsible for carrying out all cellular function. Any alteration in the gene structure results in the alteration of the genetic message. This change in structure of a gene is called as mutation and mutation can be either spontaneous or induced mutation.

Spontaneous mutation occurs as a result of failure in the process of DNA duplication, which involves steps like DNA helicase induced DNA replication where the DNA strands are separated and action of DNA polymerase in creating copies of replicated DNA strands resulting in formation of two double stranded DNAs. Misfunction of DNA polymerase contributes to mutation. Generally, spontaneous mutations are reversed by the repair mechanism using DNA repair proteins.

Induced mutation occurs as a result of exposure to various external factors like radiation, drugs, virus, pesticides, asbestos, alcohol and smoking. The agents or molecules which are responsible for mutation are called as mutagens. The various factors causing mutation are discussed in detail.

Radiation: There are two types of radiation called as ionizing radiation and non ionizing radiation. The alpha rays, beta rays, gamma rays, X-rays, cosmic rays and a part of UV rays are classified under ionizing radiation. Whereas, the non ionizing radiation includes microwaves, radio waves, infra red light and visible light. Nuclear reactors, nuclear fission and nuclear fusion reactions, radioactive elements, sun and particle accelerators are some of the sources of ionizing radiation.

Ionizing radiations have wide application in the field of medicine and agriculture. X-rays are widely used in the radiology section in hospitals and there are various radiation therapies available. In agriculture radiations are used as a pest control measure, where the male numbers are sterilized by exposing to radiation which restricts the increase in pest population. Also radiations are used in the food industry to sterilize the food and packing materials. Besides these benefits, exposure to ionizing radiation results in gene mutation. The type of radiation, the intensity of radiation and the length of exposure to radiation are the factors to be considered while analyzing mutation due to radiation. Ionizing radiation deforms the structure of the DNA by acting on the bonds through which the bases are connected. Whereas mutation is not observed when exposed to non-ionizing radiation except for some effects on body due to the thermal energy produced.

Virus: Viruses are also potential mutagens. In instances of some acquired viral infections, the virus attaches to the cell, transfer its genetic material into the cell thus altering the original gene, causing mutation. SV40 virus and Human Papilloma virus are examples of viral mutagens. Based on the type of genetic material whether DNA or RNA, a virus carries it is called as DNA virus and RNA virus accordingly. Examples of DNA viral mutagens are Hepatitis B virus and Human herpes virus. Hepatitis C virus is an example of RNA virus which causes cancer in liver by suppressing the activity of the tumor suppressing gene.

Asbestos: The common material used widely is identified as mutagen. Exposure to asbestos mutates p53 gene, thus altering the tumor suppressing role of the gene, causing lung cancer.

Pesticides: The exposure to pesticides, either by handling the pesticide or inhaling the pesticide causes gene mutation. The growth abnormalities observed in the children born to pregnant women exposed to the pesticide ‘Endosulfan’ is a good example. As a result many pesticides were banned by the government which includes Endosulfan and DDT.

Smoking and Drinking: Tobacco and alcohol also plays the role of mutagens when consumed in excess. Mutation caused by chain smoking is similar to that of the exposure to asbestos. Consumption of alcohol in excess causes sperm cell mutation contributing to genetic defects in the offspring.

All the mutations are not inheritable. It depends on the type of cell mutated, either a gene in the somatic cell or the germ cell. The mutation of genes in egg and sperm cell alters the trait of the offspring. Whereas the mutation of a gene due to exposure to UV rays from sun causes skin cancer only in the exposed individual and it is not passed on to next generation. Mutation due to the above discussed factors can be controlled by adopting various preventive measures suitable for the type of mutagen.
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#2
Gen means birth or origin, as in the book of Genesis, which explains the origin of the Earth; "Muta" means change; "terato" means monster; and "carcino" means crab. Thus, all three "gens"-are physical or chemical agents that cause or originate malformations.

Mutagens cause changes (mutations) in the genetic material of cells. Teratogens cause irreversible, deleterious structural malformations in fetuses. Some congenital malformations are so severe they result in grossly deformed fetuses. Carcinogens cause cancerous tumors with a characteristically crablike appearance.

Mutagens, teratogens and carcinogens are similar in that each causes some form of mutation. Congenital malformations can be caused by mutations, which may occur in the parent germ cell (sperm or ovum), in the resulting embryo (mutagenic effect), or in some cells of a fetus after development has begun (teratogenic effect). Mutations in somatic (body) cells can cause certain cancers (carcinogenic effect). One hypothesis for determining the etiology of chemically induced cancer involves the concept of somatic mutation, which is based on the fact that several chemicals capable of causing cancer in animals also are capable of causing mutations in microorganisms.

Mutagens. The most significant mutagenic event is transmission of heritable effects through germ cells to the next generation. Germ cells are comprised of complex structures called chromosomes. Chromosomes are composed of molecules of deoxyribonucleic acid (DNA) and are contained in cell nuclei. A gene is the smallest unit of a germ cell considered to carry a genetic message; one gene exists for each characteristic. Genes are linked together in long chains to form chromosomes.

When sufficient evidence establishes a causal connection between human exposure to a chemical and heritable genetic effects, the substance is classified as a mutagen. Mutations may occur either in somatic (body) cells or germ (reproductive) cells. Somatic mutations are inherited by other somatic cells formed from a changed cell, but they are not inherited by offspring of organisms in which a somatic mutation resides. Chemicals that can produce this type of mutation are referred to as "genotoxic." Although these agents do not damage future generations, they may initiate a biochemical rampage in cells of an affected organism. The result is a cancerous growth.

Recent studies show chemicals can cause mutations by generating rapid cell division, or mitogenesis. "A dividing cell is much more at risk of mutating," explains Bruce Ames, a research scientist at the University of California, Berkeley. "These mutations can transform normal cells into cancer cells." Non-genotoxic, or epigenetic, chemicals generally cause mutations only when administered in enormous doses. The best example is saccharin.

Teratogens. Teratogens are agents that cause abnormalities in developing organisms in the womb. When a fetal abnormality is manifested in progeny, the infant is born with a congenital defect, anomaly or malformation. Congenital abnormalities also may result from other factors. Human congenital abnormalities may stem from diseases mothers may have during the first trimester of pregnancy, particularly such viral diseases as German measles (rubella).

Carcinogens. Carcinogens can cause malignant tumors. However, a distinction between benign and malignant tumors is not always possible. Nevertheless, the mark of carcinogenicity is an increase in malignant tumors. For a chemical to be considered a human carcinogen under expected conditions of exposure, it also must be genotoxic.
Studies show that up to 90 percent of all mutagens are carcinogens. The theory that mutation sets the stage for cancer development is based on the fact that many mutagenic physical and chemical agents also are carcinogenic. Mutations giving rise to cancer usually occur in somatic cells. If a change caused by such mutations is minor, it probably never will be discovered. However, if there is a major change, the cell may die.
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Understanding Mutagens responsible for Mutation00