MoBio Mutation by Chemical Agents Chapter 7

The chemical agents which may cause mutation are called mutagens. Most of them are also carcinogens. The following figure shows the chemical structures of a few potent mutagens. Figure 7-F-7 explains the mechanism of mutation by 5-bromouracil.

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Figure 7-F-6. Structures of potent mutagens.

  • Acridines (e.g., proflavin) are positively charged molecules. They may be inserted between two DNA strands, thereby altering DNA's structure and rigidity. As a result, DNA replication will not be faithful.
  • Alkylating agents are chemicals that add an alkyl group (CnH2n+1) to another molecule. Alkylation of a base may change the normal base pairing. For example, the alkylating agent EMS converts guanine to 7-ethylguanine which pairs with thymine. The mispairing will lead to mutation. Some alkylating agents may also cross-link DNA, resulting in chromosome breaks.
  • Nitrous acid is a deaminating agent that converts cytosine to uracil, adenine to hypoxanthine, and guanine to xanthine. The hydrogen-bonding potential of the modified base is altered, resulting in mispairing.
  • Hydroxylamine and free radicals may modify base structures, resulting in mispairing.
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Figure 7-F-7. Mechanism of mutation induced by 5-bromouracil. This molecule has two tautomeric isoforms. Its keto form (BUk) pairs with adenine whereas its enol form (BUe) pairs with guanine. Suppose in the first replication the keto form was incorporated into a new DNA strand. During the second replication, if the keto form undergoes a tautomeric shift to the enol form, it will cause A:T to G:C mutation.

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Figure 7-F-8. (a) Base structures induced by free radicals. (b) The base change induced by NH2OH.