The Ames Test: How Bruce Ames used bacteria to solve the mystery of the murderous mutagen

Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Ames BN, Durston WE, Yamasaki E, Lee FD. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281-5. doi: 10.1073/pnas.70.8.2281. OTHER VIDEOS YOU MIGHT LIKE: • Mutant flies helped us discover intragenic recombination -    • Mutant flies helped us discover intragenic...   • The evolutionary origins of the baker’s yeast Saccharomyces cerevisiae -    • The evolutionary origins of the baker’s ye...   • The genetics of citrus - Where do they come from? -    • The genetics of citrus - Where do they com...   Ever wondered why some chemicals are considered to be ‘safe’ while others are termed as deadly ‘carcinogens’? How did we come to these definitions and how can we reliably weed out the seemingly endless amounts of chemicals to indeed find our mutagenic culprit? Well, in the early 1970s, the renowned American biochemist Bruce Ames devised the Ames Test that could in fact allow us to identify mutagenic chemicals once and for all! His use of mutated strains of Salmonella Typhimurium laid the groundwork for an improvement to his original system, extending its reach to account for not only bacteria, but for mammals and humans. The original system used multiple tester strains, each with their own mutation that affected the His operon – a group of genes responsible for synthesising histidine, a crucial amino acid needed for growth and proliferation. This rendered the bacteria unable to grow in culture, showing growth deficiency. Ames saw that the carcinogens that he tested that were in fact mutagenic, were able to revert the original mutations present within each of the tester strains, allowing the bacteria to once again synthesise histidine and thus grow on the plates! So now for the cool part; by adding rat and human liver homogenate into the mix, this allows us to simulate the metabolic action of an organism, seeing if Ames’ test could not only talk the talk, but walk the walk. Alas, Ames saw similar results to his originally pure bacterial test, showing that it was in fact the liver homogenate that was responsible for activating these carcinogens, forming the murderous mutagenic suspects. In fact, it was the chemical structure of each of the carcinogens that allowed them to intermingle with the DNA to cause additional alteration to the sequences. Today, in diagnostic labs around the world, the Ames test is still used to characterise potentially harmful chemicals in the pharmaceutical industry. For this extreme level of regulation and safety, we have only one man to thank – one of the greatest biochemical detectives ever, Bruce Ames. Creator: Luka Biskupovich References: Ames BN, Durston WE, Yamasaki E, Lee FD. Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection. Proc Nat Acad Sci USA. 1973;70(8):2281-2285. Ames BN, Lee FD, Durston WE. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Nat Acad Sci USA. 1973;70(3):782-786. Hartman PE, Hartman Z, Stahl RC, Ames BN. Classification and mapping of spontaneous and induced mutations in the histidine operon of Salmonella. Adv Genet. 1971;16:1-34. Imray FP, Macphee DG. Spontaneous and induced mutability or frameshift strains of Salmonella typhimurium carrying uvrB and polA mutations. Mutat Res. 1976;34(1):35-42. Miller EC, Miller JA. Mechanisms of chemical carcinogenesis. Cancer. 1981;47:1055-1064. Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzaghi E, Inouye M. Frameshift mutations and the genetic code. Cold Spring Harb Symp Quant Biol. 1966;31:77-84.