High-dose-level effects in mutagenicity assays utilizing mammalian cells in culture. 1988

A H Seeberg, and P Mosesso, and R Forster
Life Science Research Roma Toxicology Centre, Italy.

We report here results obtained using sodium chloride and potassium chloride as model compounds to investigate the effects of high dose levels and osmolarity-mediated artefacts in mutagenicity assays using cultured mammalian cells. Three assay systems were used with different genetic end-points: (i) mutation to 6-thioguanine resistance in Chinese hamster V79 cells; (ii) induction of chromosome aberrations in Chinese hamster ovary cells; and (iii) induction of unscheduled DNA synthesis in HeLa S3 cells. In V79 cells we observed sporadic increases in mutation frequency after treatment with sodium chloride. Potassium chloride increased the mutation frequency in a narrow interval of dose levels. Chromosome aberrations were induced by both compounds at the highest concentrations tested, confirming previously published data; the effects of potassium chloride were more marked. The chromosome aberrations observed included both deletions and exchange figures. Neither compound induced UDS in our experiments. We performed the Ames test as a check for mutagenic contaminants and both compounds gave entirely negative results. Although the osmolarities of sodium chloride and potassium chloride solutions were similar, the effects of potassium chloride were always greater at equivalent concentrations; the nature of the solute, and not only the observed osmolarity, appears to influence the results obtained. Similarly, we have observed that dimethylsulphoxide causes a marked increase in the osmolarity of the culture medium without any obvious induction of chromosome aberrations. Although the presence of S9 had little effect on the osmolarity of the medium, differences in response were observed after treatments with or without S9. For the two model compounds it appears that an osmotic mechanism alone does not provide a sufficient explanation of the findings.

UI MeSH Term Description Entries
D008297 Male Males
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009994 Osmolar Concentration The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D011189 Potassium Chloride A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA. Slow-K,Chloride, Potassium
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012965 Sodium Chloride A ubiquitous sodium salt that is commonly used to season food. Sodium Chloride, (22)Na,Sodium Chloride, (24)NaCl

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