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Molecular Principles Underlying the Ames Salmonella/Microsome Test: Elements and Design of Short-Term Mutagenesis Tests

  • Graham Walker

Abstract

The drug resistance plasmid pKM101 has played a critical role in the success of the Ames Salmonella tester strains in detecting carcinogens as mutagens. pKM101 increases the susceptibility of bacterial cells to both point and frameshift mutagenesis by a variety of chemical mutagens and makes them more resistant to killing by ultraviolet light. It does so in a recA + lexA +-dependent fashion and suppresses the mutagenesis and repair deficiencies of Escherichia coli umuC mutants, suggesting that the plasmid codes for protein(s) which participate in the process of “error-prone repair.” In the absence of pKM101, Salmonella typhimurium appears to be less proficient than Escherichia coli in its capacity to carry out “error-prone repair”; but if pKM101 is present, both have similar capacities. In addition, much of this capacity to process chemical damage and give mutations is constitutively expressed in pKM101-containing cells. pKM101 is able to increase the frequencies of both transitions and transversions in response to chemical mutagens. Point mutants of pKM101 have been isolated which have concomitantly lost the ability to increase base-pair substitution and frameshift mutagenesis and to protect cells against killing by UV. Recently, we have isolated pKM101 mutants with similar properties by insertion of the translocatable drug resistance element Tn5. All such insertions were shown to map within a ca. 1500 bp region of pKM101. Genetic experiments suggest that at least two pKM101-coded functions are involved in the enhancement of chemical mutagenesis.

Keywords

AMES Test Chemical Mutagen Chemical Mutagenesis Methyl Methanesulfonate Base Substitution Mutagen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Graham Walker
    • 1
  1. 1.Biology DepartmentMassachusetts Institute of TechnologyCambridgeUSA

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