DNA-cell-binding (DCB) assay for suspected carcinogens and mutagens.
This report describes a novel technique for screening potential carcinogens and mutagens. The DNA-cell-binding (DCB) assay is based on earlier observations which indicated that DNA and other nucleic acids exposed to active carcinogens strongly react with other macromolecules, producing nucleic acid--nucleic acid and nucleic acid--protein adducts. The latter group of adducts included complexes with proteins present in both prokaryotic and eukaryotic cell membranes. Increased attachment of DNA to the intact bacterial and animal cells was seen in the presence of active carcinogens or carcinogens activated by extracts from mouse and rat livers. We have conducted a survey of almost 280 chemicals including 130 with known carcinogenic potential (i.e., either known carcinogens or known non-carcinogens). The DCB test and animal assays agreed in abut 96% of cases. Thus, as a predictor of potential carcinogenicity, this assay compares favorably with other rapid methods currently in use. In this respect, the DCB assay is also superior to other techniques which measure the formation of macromolecular complexes, such as velocity centrifugation through sucrose gradients, gel electrophoresis, filtration through nitrocellulose filters, chromatography on methyl-esterified albumin, equilibrium density gradient centrifugation, etc. In the few cases for which the data were available, combining the results of DCB assays with the results of experiments in which the induction of DNA--protein adducts in living human cells in tissue culture has been measured by cold phenol extraction, the predictability was increased to 100%. We suggest that DCB assay should be used either alone or in combination with other rapid methods of carcinogen detection for screening industrial, environmental and other chemicals and chemical mixtures for their carcinogenic potential. Ways of further improving and simplifying the DCB tests are considered.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D002478:Cells, Cultured / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens; D011485:Protein Binding
D002273:Carcinogens; D004269:DNA, Bacterial; D046911:Macromolecular Substances; D009153:Mutagens; D004247:DNA