Practical and theoretical aspects of the DCB assay for carcinogenic and other genotoxic agents

Autor: H. Kubinski, Z. O. Kubinski
Rok vydání: 1986
Předmět:
Zdroj: Toxicity Assessment. 1:387-406
ISSN: 1098-2256
0884-8181
DOI: 10.1002/tox.2540010402
Popis: The DNA-cell binding (DCB) assay grew from our early studies demonstrating that in the presence of carcinogenic chemicals, radioactively labeled nucleic acids attached strongly to isolated cellular membranes and to intact prokaryotic and eucaryotic cells. A survey of over 300 chemicals revealed that this test is capable of correctly predicting carcinogenic potential in more than 95% of cases. Recently we began using formaldehyde-treated Escherichia coli indicator cells and noted that the accuracy of prediction and the sensitivity of the test are even greater. For example, a class of noncarcinogenic, intercalating agents that showed as false positives in the original study, scored negative in this modified version of DCB test. This assay has several advantages over other rapid tests for genotoxicity, including simplicity, rapidity, economy, and reproducibility. As demonstrated by our studies on a number of diverse products, it is especially suitable for analyzing industrial and other environmental chemicals and their mixtures. The increased DNA-cell binding is due to a property shared by most, if not all, carcinogenic agents—their ability to produce macromolecular adducts between proteins and nucleic acids, as well as inter- and intramolecular complexes in DNA. The latter class of adducts is responsible for inducing chromosomal transposition-like events that we observed in a separate set of experiments using transformation of Bacillus subtilis for measuring distances between genetic markers. In these experiments markers were stably transferred to a different position on the chromosome as the result of DNA-exposure to an ultimate carcinogen, N-acetoxy N-acetyl-aminofluorene. If, as many investigators believe, the specific chromosomal translocations are the cause of neoplasia, the high predictive potential of the DCB test may be due to its capability to measure the production of specific macromolecular complexes.
Databáze: OpenAIRE
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