The Ames Test in Twenty-first Century

Abstract

Since the 19th century, industrial development has increased exposure to mutagens and possible carcinogens. In order to avoid these health risks, several techniques have been developed to recognize genotoxins. In the 1970s, Dr. Bruce Ames and colleagues, studying the histidine operon of Salmonella typhimurium, observed that histidine (−) auxotroph mutants were reverted to histidine (+) upon exposure to a mutagen. The researchers further observed that known carcinogens were mutagenic to S. typhimurium strains. The Ames test has since been employed as a first step in evaluating genotoxic risk. The Ames method has been accepted by several international organizations including the IARC (International Agency of Cancer Research), EPA (Environmental Protection Agency), FDA (Food and Drug Administration), IVGT (In Vitro Genetic Toxicity Testing Project), REAC (European Union Legislation, Registration, Evaluation, Authorization and Restriction of Chemicals), and the Japanese Ministry of Health and Welfare (MHW). Occasionally, research of new products is suspended upon a positive Ames test result. The Ames test has also been improved to evaluate DNA repair mechanisms using S. typhimurium uvrB + /uvrB− strains. Additionally, researchers have genetically modified these strains to investigate metabolic mechanisms that convert pre-mutagens to active mutagens. The Ames test has also been useful for studying alternatives to reduce genotoxic risk. It is widely employed for antimutagenic evaluation and elucidation of their mechanisms of action. Knowledge on antimutagens is important to reduce mutagenic risk of genotoxic compounds which cannot be avoided, such as therapeutic drugs. A major pitfall of the Ames test is the correlation of data obtained from prokaryotic cells and eukaryotic cells. The aim of this review is to analyze the advantages of the Ames test as a method for studying several aspects of genetic toxicology.