51. The modulating effect of ATM, ATR, DNA-PK inhibitors on the cytotoxicity and genotoxicity of benzo[a]pyrene in human hepatocellular cancer cell line HepG2
- Author
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Magdalena Ferlińska, Anna Smok-Pieniążek, Joanna Roszak, Maciej Stępnik, Marek Nocuń, and Sylwia Spryszyńska
- Subjects
animal structures ,DNA damage ,Cell Survival ,Health, Toxicology and Mutagenesis ,Morpholines ,Apoptosis ,Ataxia Telangiectasia Mutated Proteins ,Biology ,Protein Serine-Threonine Kinases ,Toxicology ,medicine.disease_cause ,complex mixtures ,chemistry.chemical_compound ,Caffeine ,polycyclic compounds ,medicine ,Benzo(a)pyrene ,Humans ,Cytotoxicity ,Protein Kinase Inhibitors ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,Liver Neoplasms ,General Medicine ,Glutathione ,Hep G2 Cells ,Molecular biology ,Comet assay ,Biochemistry ,chemistry ,Chromones ,Pyrones ,Genotoxicity ,DNA Damage - Abstract
The effect of inhibitors of phosphatidylinositol-3-kinase-related kinases (PIKK): ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) on response of HepG2 human liver cancer cells to benzo[a]pyrene (BaP) was investigated. PIKK inhibitors: KU55933 (5 μM), NU7026 (10 μM) or caffeine (1 and 2mM) when used as single agents or in combinations (KU55933/NU7026 and caffeine/NU7026) did not significantly influence the BaP (3 μM) cytotoxicity (MTT reduction test). BaP induced a weak proapoptotic effect which was moderately enhanced by both inhibitor combinations. HepG2 cells exposed to BaP showed a strong S-phase arrest which was considerably diminished by both inhibitor combinations. The DNA damage (comet assay) induced after continuous 24h exposure to BaP was significantly diminished by both inhibitor combinations. Weak induction of reactive oxygen species by BaP was observed, which was not modulated by the inhibitor combinations. Similarly, no modulation of the glutathione levels was observed.
- Published
- 2015