The DRAG test: an assay for detection of genotoxic damage.
A high throughput assay (the DRAG test) is described, which could be a useful tool for the detection of repairable DNA adducts, and which is based on the inhibition of the growth of DNA repair-deficient Chinese hamster ovary (CHO) cells. The cytotoxicity of a test substance towards DNA repair-deficient CHO cell lines is compared with the corresponding cytotoxicity in the parental wild-type CHO cell line (AA8). A more pronounced toxicity toward a DNA repair-deficient cell line is interpreted as being the consequence of its inability to repair the DNA adduct induced by the compound. (+)-7beta,8alpha-Dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, camptothecin, ethyl methanesulphonate and mitomycin C were used as reference substances, and the overall results indicate that the DRAG test could be useful in the screening of compounds for the production of repairable DNA adducts. The main advantages with the DRAG test are that it provides a relevant endpoint, it is rapid, it requires small amounts of the test item, and it permits a large number of compounds to be tested.
Helleday
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Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, 106 91 Stockholm, Sweden.
Johansson
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Jenssen
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D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000818:Animals; D016466:CHO Cells; D002166:Camptothecin / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008698:Mesylates / Q000633:toxicity; D016685:Mitomycin / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity; D012015:Reference Standards
D002273:Carcinogens; D018736:DNA Adducts; D008698:Mesylates; D009153:Mutagens; C045880:methanesulfonic acid; D016685:Mitomycin; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D002166:Camptothecin