Proceedings of the National Academy of Sciences · 1973 · 2.3K citations · 20 references
PharmacyMolecular BiologyToxicologyCarcinogenesisGenetic ToxicologyMolecular ToxicologyCarcinogen MetabolismCarcinogenic MechanismsCarcinogenicity AssessmentChemical CarcinogenesisChemical MutagenesisMutagenicity AssessmentCarcinogen-dna InteractionsChemical Mutagen ScreeningFrameshift Mutation InductionFrameshift MutationsMammalian Cell Mutagenicity AssaysMechanisms Of CarcinogenicityMutagenesis ScreeningMutagenic Mechanisms
Carcinogens such as aflatoxin B1, benzo(a)pyrene, acetylaminofluorene, benzidine, and dimethylamino‑trans‑stilbene are activated by liver homogenates to form potent frameshift mutagens, a process linked to planar ring systems and metabolizable reactive groups that facilitate somatic mutation. The authors propose that these carcinogens, and many other mutagens, cause cancer through somatic mutation. They describe a simple, inexpensive, highly sensitive assay that combines a rat or human liver homogenate for metabolic activation with Salmonella histidine mutants and a TPNH‑generating system, all incubated together on a petri plate. The assay detects as little as a few nanograms of the most active compounds.
18 Carcinogens, including aflatoxin B(1), benzo(a)pyrene, acetylaminofluorene, benzidine, and dimethylamino-trans-stilbene, are shown to be activated by liver homogenates to form potent frameshift mutagens. We believe that these carcinogens have in common a ring system sufficiently planar for a stacking interaction with DNA base pairs and a part of the molecule capable of being metabolized to a reactive group: these structural features are discussed in terms of the theory of frameshift mutagenesis. We propose that these carcinogens, and many others that are mutagens, cause cancer by somatic mutation. A simple, inexpensive, and extremely sensitive test for detection of carcinogens as mutagens is described. It consists of the use of a rat or human liver homogenate for carcinogen activation (thus supplying mammalian metabolism) and a set of Salmonella histidine mutants for mutagen detection. The homogenate, bacteria, and a TPNH-generating system are all incubated together on a petri plate. With the most active compounds, as little as a few nanograms can be detected.
20
Chemical Mutagens. Principles and Methods for Their Detection.
Annals of Internal Medicine · 1974 · 1.5K citations
Pharmacy, Microbiology, Toxicology +17
Frameshift Mutations and the Genetic Code
George Streisinger, Yasushi Okada, Joyce Emrich et al. · Cold Spring Harbor Symposia on Quantitative Biology · 1966 · 1.4K citations