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Author DeMarini, D. M. ♦ Cros, S. ♦ Paoletti, C. ♦ Lecointe, P. ♦ Hsie, A. W.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT. ♦ ANTINEOPLASTIC DRUGS ♦ CARCINOGEN SCREENING ♦ MUTAGEN SCREENING ♦ ANIMAL CELLS ♦ CELL KILLING ♦ CHEMICAL BONDS ♦ CHO CELLS ♦ COVALENCE ♦ DNA REPLICATION ♦ ENZYME ACTIVITY ♦ EXPERIMENTAL DATA ♦ HAMSTERS ♦ METABOLIC ACTIVATION ♦ MUTAGENESIS ♦ REVERTANTS ♦ SALMONELLA ♦ STRUCTURE-ACTIVITY RELATIONSHIPS ♦ TOXICITY ♦ ANIMALS ♦ BACTERIA ♦ DATA ♦ DRUGS ♦ INFORMATION ♦ MAMMALS ♦ MICROORGANISMS ♦ MUTANTS ♦ NUCLEIC ACID REPLICATION ♦ NUMERICAL DATA ♦ RODENTS ♦ SCREENING ♦ VERTEBRATES ♦ Chemicals Metabolism & Toxicology- Cells- (-1987) ♦ Chemicals Metabolism & Toxicology- Microorganisms- (-1987)
Abstract The mutagenicity and cytotoxicity of five antitumor compounds (ellipticines) were investigated in the Chinese hamster ovary cell hypoxanthine-guanine phosphoribosyltransferase assay and in six strains of Salmonella. All five compounds (ellipticine, 9-methoxyellipticine, 9-hydroxyellipticine, 9-aminoellipticine, and 2-methyl-9-hydroxyellipticinium) were cytotoxic and mutagenic in the Chinese hamster ovary cell hypoxanthine-guanine phosphoribosyltransferase assay in the presence or absence of Aroclor 1254-induced rat liver S9, and all except the last compound were mutagenic in Salmonella. Based on the reversion pattern obtained in various frame-shift and DNA repair-proficient (uvrB/sup +/) or -deficient (uvrB) strains of Salmonella in the presence or absence of S9, the first three compounds appear to cause frameshift mutations by both intercalation and covalent bonding with DNA; thus, these are classified as reactive intercalators. However, 9-aminoellipticine intercalates only weakly and may instead exert its mutagenic activity primarily (or exclusively) by forming a covalent adduct with DNA. Compared to the published antitumor data obtained in mice, the results in Salmonella and Chinese hamster ovary cells suggest that the ability of ellipticine, 9-methoxyellipticine, and 9-hydroxyellipticine to intercalate with DNA, induce frame-shift mutations, and cause cell killing is associated with and may be the basis for their antitumor activity. The observation that the ellipticines are mutagenic in mammalian cells suggests that these antitumor agents may be carcinogenic.
Educational Use Research
Learning Resource Type Article
Publisher Date 1983-08-01
Publisher Place United States
Journal Cancer Res.
Volume Number 43
Organization Univ. of Tennessee-Oak Ridge Graduate School of Biomedical Sciences


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