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  • In vitro DNA-damaging effects of intestinal and related tetrapyrroles in human cancer cells

    Author(s)
    Moelzer, Christine
    Pfleger, Barbara
    Putz, Elisabeth
    Rossmann, Antonia
    Schwarz, Ursula
    Wallner, Marlies
    Bulmer, Andrew C
    Wagner, Karl-Heinz
    Griffith University Author(s)
    Bulmer, Andrew C.
    Wagner, Karl-Heinz
    Year published
    2013
    Metadata
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    Abstract
    Epidemiological studies report a negative association between circulating bilirubin concentrations and the risk for cancer and cardiovascular disease. Structurally related tetrapyrroles also possess in vitro anti-genotoxic activity and may prevent mutation prior to malignancy. Furthermore, few data suggest that tetrapyrroles exert anti-carcinogenic effects via induction of cell cycle arrest and apoptosis. To further investigate whether tetrapyrroles provoke DNA-damage in human cancer cells, they were tested in the single cell gel electrophoresis assay (SCGE). Eight tetrapyrroles (unconjugated bilirubin, bilirubin ditaurate, ...
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    Epidemiological studies report a negative association between circulating bilirubin concentrations and the risk for cancer and cardiovascular disease. Structurally related tetrapyrroles also possess in vitro anti-genotoxic activity and may prevent mutation prior to malignancy. Furthermore, few data suggest that tetrapyrroles exert anti-carcinogenic effects via induction of cell cycle arrest and apoptosis. To further investigate whether tetrapyrroles provoke DNA-damage in human cancer cells, they were tested in the single cell gel electrophoresis assay (SCGE). Eight tetrapyrroles (unconjugated bilirubin, bilirubin ditaurate, biliverdin, biliverdin-/bilirubin dimethyl ester, urobilin, stercobilin and protoporphyrin) were added to cultured Caco2 and HepG2 cells and their effects on comet formation (% tail DNA) were assessed. Flow cytometric assessment (apoptosis/necrosis, cell cycle, intracellular radical species generation) assisted in revealing underlying mechanisms of intracellular action. Cells were incubated with tetrapyrroles at concentrations of 0.5, 5 and 17 占for 24 h. Addition of 300 占tertiary-butyl hydroperoxide to cells served as a positive control. Tetrapyrrole incubation mostly resulted in increased DNA-damage (comet formation) in Caco2 and HepG2 cells. Tetrapyrroles that are concentrated within the intestine, including protoporphyrin, urobilin and stercobilin, led to significant comet formation in both cell lines, implicating the compounds in inducing DNA-damage and apoptosis in cancer cells found within organs of the digestive system.
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    Journal Title
    Experimental Cell Research
    Volume
    319
    Issue
    4
    DOI
    https://doi.org/10.1016/j.yexcr.2012.12.003
    Subject
    Cancer Cell Biology
    Biochemistry and Cell Biology
    Clinical Sciences
    Publication URI
    http://hdl.handle.net/10072/54168
    Collection
    • Journal articles

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