IN VITRO TOXICOLOGY Cellular Toxicology Joura of Molecular and Volumc 2, Number 1988 Mary Ann Lieben, Inc . Publishers DNA Conformation Assay: Determination of In Vitro DNA Adduct Formation and Strand Breaks MULLER, S YEATS and U. LINZ R.-A_ WALK T. INBIFO Institut flir biologische Forschung D-SOOO Koln 9 FRG ABSTRACT detected by the conversion The DNA strand breaks appear ance supercoiled (pBR322 ) its relaxed circular conformation plasnid DA open was and mutagenic the genotoxic ptential 28 nonmutagenic (including used test and indirect-act ing) model chemicals. This very rapid and simple in vitro direct- chemicals which not shorn useful for the detect io assay their metabolic for interactio with DMA , because DNA require act ivation nu- ethylendianinetetraacetic acid clease-depleted microsones the presence to efficiently activate indirect-acting found chemicals ultimate (EDTA ) were reactive species. cmnformation is a least Tne results showed that the DNA assay sensitive specific the Salmonella mutatio (Ames) assay . and reverse (obtained fram caparison to in vivo carcinogenicity data Gene-Tox data base the (17 23 chemicals Nesnoy 1986) indicated that out al. accuracy Tne achieved. crrectly ident ified carcinogens noncarcinogens) Kas were quick accuracy perforance the DNA conformation together with its and easy make screening of chemicals for their useful thod for che short-term assay genotoxic potent ial HIGILX CONFIDENTLAL INFORMATION produced by Phlllp Monk _ qublec Phlllp Monily AEG rounordsr hldocunicnt contcnu Ihall not br uicd, thotmn Lhc coun' uder. durbuled iccpl pruldrd metabolic Keywords: genotoxic chemicals, strand breaks short-term assay , DNA act ivation 20316930 ;0
IN VITRO TOXICOLOGY Joura of Molecular and Cellular Toxicology Volumc 2, Number 1988 Mary Ann Lieben, Inc . Publishers DNA Conformation Assay: Determination of In Vitro DNA Adduct Formation and Strand Breaks R.-A_ WALK T. MULLER, S YEATS and U. LINZ INBIFO Institut flir biologische Forschung D-SOOO Koln 9 FRG ABSTRACT The appear ance DNA strand breaks detected by the conversion supercoiled plasnid DA (pBR322 ) its relaxed open circular conformation was used test the genotoxic ptential 28 nonmutagenic and mutagenic (including direct- and indirect-act ing) model chemicals. This very rapid and simple in vitro assay shorn useful for the detect io chemicals which not require metabolic act ivation for their interactio with DMA , because DNA nu- clease-depleted microsones the presence ethylendianinetetraacetic acid (EDTA ) were found to efficiently activate indirect-acting chemicals ultimate reactive species. Tne results showed that the DNA cmnformation assay is a least sensitive and specific the Salmonella reverse mutatio (Ames) assay . caparison to in vivo carcinogenicity data (obtained fram the Gene-Tox data base Nesnoy al. 1986) indicated that accuracy (17 out 23 chemicals were crrectly ident ified carcinogens noncarcinogens) Kas achieved. Tne accuracy together with its quick and easy perforance make the DNA conformation assay useful thod for che short-term screening of chemicals for their genotoxic potent ial HIGILX CONFIDENTLAL INFORMATION produced by Phlllp Monk _ qublec rounordsr Phlllp Monily AEG hldocunicnt contcnu Ihall not br uicd, thotmn durbuled iccpl pruldrd Lhc coun' uder. Keywords: genotoxic chemicals, short-term assay , DNA strand breaks metabolic act ivation 20316930 ;0