Chemically Induced Mutations

Although many mutations arise spontaneously, a number of environmental agents are capable of damaging DNA, including certain chemicals and radiation. Any environmental agent that significantly increases the rate of mutation above the spontaneous rate is called a mutagen.

The first discovery of a chemical mutagen was made by Charlotte Auerbach, who was born in Germany to a Jewish family in 1899. After attending university in Berlin and doing research, she spent several years teaching at various schools in Berlin. Faced with increasing anti-Semitism in

Nazi Germany, Auerbach immigrated to Britain, where she conducted research on the development of mutants in Drosophila. There she met Herman Muller, who had shown that radiation induces mutations; he suggested that Auerbach try to obtain mutants by treating Drosophila with chemicals. Her initial attempts met with little success. Other scientists were conducting top-secret research on mustard gas (used as a chemical weapon in World War I) and noticed that it produced many of the same effects as radiation. Auerbach was asked to determine whether mustard gas was mutagenic.

Collaborating with pharmacologist J. M. Robson, Auerbach studied the effects of mustard gas on Drosophila melanogaster. The experimental conditions were crude. They heated liquid mustard gas over a Bunsen burner on the roof of the pharmacology building, and the flies were exposed to the gas in a large chamber. After developing serious burns on her hands from the gas, Auerbach let others carry out the exposures, and she analyzed the flies. Auerbach and Robson showed that mustard gas is indeed a powerful mutagen, reducing the viability of gametes and increasing the numbers of mutations seen in the offspring of exposed flies. Because the research was part of the secret war effort, publication of their findings was delayed until 1947. A brief history of Herman Muller

Base analogs One class of chemical mutagens consists of base analogs, chemicals with structures similar to that of any of the four standard bases of DNA. DNA polymerases cannot distinguish these analogs from the standard bases; so, if base analogs are present during replication, they may be incorporated into newly synthesized DNA molecules. For example, 5-bromouracil (5BU) is an analog of thymine; it has the same structure as that of thymine except that it has a bromine (Br) atom on the 5-carbon atom instead of a methyl group (Figure 17.18a). Normally, 5-bromouracil pairs with adenine just as thymine does, but it occasionally mispairs with guanine (Figure 17.18b), leading to a transition (T-A:5BU-A:5BU-G:C-G), as shown in

Normal base h3c o

Base analog

Br O

Normal base h3c o

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