Comparison of passive-dosed and solvent spiked exposures of pro-carcinogen, benzo[a]pyrene, to human lymphoblastoid cell line, MCL-5
| Autor: | Gareth J.S. Jenkins, Fiona M. Chapman, David J. Sanders, Chris Sparham, Andrew D. Scott, Roger van Egmond, Katherine E. Chapman, Shareen H. Doak, Colin Hastie |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Toxicology medicine.disease_cause Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Benzo(a)pyrene Humans Dimethyl Sulfoxide Carcinogen Aqueous solution Chromatography Micronucleus Tests Chemistry Cell Cycle Aqueous two-phase system General Medicine Solvent 030104 developmental biology 030220 oncology & carcinogenesis Carcinogens Solvents Pyrene Micronucleus Genotoxicity DNA Damage |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 67 |
| ISSN: | 1879-3177 |
| Popis: | Genotoxicity testing methods in vitro provide a means to predict the DNA damaging effects of chemicals on human cells. This is hindered in the case of hydrophobic test compounds, however, which will partition to in vitro components such as plastic-ware and medium proteins, in preference to the aqueous phase of the exposure medium. This affects the freely available test chemical concentration, and as this freely dissolved aqueous concentration is that bioavailable to cells, it is important to define and maintain this exposure. Passive dosing promises to have an advantage over traditional ‘solvent spiking’ exposure methods and involves the establishment and maintenance of known chemical concentrations in the in vitro medium, and therefore aqueous phase. Passive dosing was applied in a novel format to expose the MCL-5 human lymphoblastoid cell line to the pro-carcinogen, benzo[a]pyrene (B[a]P) and was compared to solvent (dimethyl sulphoxide) spiked B[a]P exposures over 48 h. Passive dosing induced greater changes, at lower concentrations, to micronucleus frequency, p21 mRNA expression, cell cycle abnormalities, and cell and nuclear morphology. This was attributed to a maintained, definable, free chemical concentration using passive dosing and the presence or absence of solvent, and highlights the influence of exposure choice on genotoxic outcomes. |
| Databáze: | OpenAIRE |
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