Frameshift mutations can be caused by intercalating agents. These are chemical agents that insert between adjacent base pairs (like inserting between the rungs of a ladder). The intercalation causes a conformational change in the double helix, so that when replication occurs, the aberrant conformation causes small deletions or insertions to occur in the newly synthesized DNA.

Radiation

Radiation is also capable of inducing mutations in DNA. Ionizing radiation, such as gamma rays and X-rays, depending on the energy of the radiation, can create free radicals that result in prblems ranging from point mutations to chromosome breaks.

Ultraviolet (non-ionizing) radiation can cause mutations as well. The primary effect of UV on DNA is the creation of thymine dimers. Thymine dimers occur when two thymines are adjacent on a strand of DNA. UV radiation can cause the formation of a covalent bond between the two thymines, which prevents their participation in base pairing. Thymine dimers are very deleterious to a cell - they can completely interrupt replication, effectively causing a cell to die. As we'll see later in this module, one of the last-chance mechanisms of repair of thymine dimers causes the insertion of random nucleotides in place of the region containing the thymine dimer, resulting in several base substitutions at once.

Screening for Mutagenicity

Many chemicals found in the environment (both natural and synthetic) are capable of causing mutations. It is useful to know whether a particular substance is mutagenic (able to cause an increase in the mutation rate), because many mutagens are also carcinogens (cancer causing agents). This is because cancer is generally caused by mutations in genes that control cell division.

Chemical compounds are tested for mutagenicity using the Ames test. This test uses auxotrophic (mutant) strains of the bacterium Salmonella typhimurium that require medium supplemented with histidine in order to grow. The bacteria are exposed to the compound being tested, then plated on minimal medium (with no histidine). Only bacteria that underwent a reverse mutation, allowing them to synthesize their own histidine, would be able to grow under these conditions. The more mutagenic a compound is, the more likely such a reverse mutation would be. Therefore the bacteria growing on minimal medium can be counted, and this gives a relative measure of how mutagenic a compound is. Using this technique, a 90% correlation has been observed between mutagenicity and carcinogenicity.

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