Bruce Ames Contribution In Oncology

                                                           

                                           Ames Test 

Bruce Ames develops a method to  test the chemicals for cancer causing properties .  The test is based on the fact that  any thing that is mutagenic may also turn out to be a carcinogen, that is to cause cancer .
The assay is based on the reversion of the mutation in the histidine operon in the genetically altered tester strains of bacterium Salmonella typhimurium . The his peron encodes enzymes required for the biosynthesis of the amino acid hitsidine . Strains with mutations in the his operon are histidine auxotrophs . However , the mutation can be reversed , a back mutation , with the gene regaining its function . These revertants are able to grow on a medium lacking histidine . The tester strains are specially constructed to have both  frame shift and point mutation in the genes required to synthesize histidine , which allows for the detection of mutagens acting via different mechanism . The tester strains also carry  mutations in the genes responsible for lipopolysaccharide synthesis , making the cell wall of the bacteria more permeable , and in the excision repair system to make the test more sensitive .

The Ames test can detect mutagens that work directly to alter DNA . In human , however , many chemicals  are promutagens , agents that must be activated to become true mutagens . Activation , involving a chemical modification , often  occurs in the liver as a consequences of normal liver activity on unusual substance . Bacteria such as S. typhimurium do not produce the enzyme required to active  promutagens , so promutagens would not be detected by the Ames test unless there were first activated .