No induction of structural chromosomal aberrations in cylindrospermopsin-treated CHO-K1 cells without and with metabolic activation
Cylindrospermopsin (CYN) is a cyanobacterial alkaloid that has been implicated in outbreaks of human morbidity and animal mortality. The principal mode of action for CYN is inhibition of protein and glutathione synthesis, and its toxicity seems to be mediated by cytochrome P-450-generated metabolite...
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Published in | Toxicon (Oxford) Vol. 50; no. 8; pp. 1105 - 1115 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
15.12.2007
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | Cylindrospermopsin (CYN) is a cyanobacterial alkaloid that has been implicated in outbreaks of human morbidity and animal mortality. The principal mode of action for CYN is inhibition of protein and glutathione synthesis, and its toxicity seems to be mediated by cytochrome P-450-generated metabolites. It was also shown that CYN might be responsible for tumor initiation in animals; nevertheless, mechanisms leading to CYN-induced carcinogenesis are scarce and equivocal. The aim of the present study was to investigate the impact of metabolic activation on CYN-induced DNA damage. The effect of different doses of CYN (0.05–2
μg/ml) on DNA damage was determined in CHO-K1 cells after 3, 16 and 21
h of the treatment. The chromosome aberration assay with and without metabolic activation was applied to evaluate the clastogenic activity of CYN and its metabolite(s). In addition, the occurrence of apoptosis and necrosis was estimated by the annexin method using flow cytometry. The results revealed that CYN is not clastogenic in CHO-K1 cells irrespective of S9 fraction-induced metabolic activation. However, CYN significantly decreases the frequencies of mitotic indices and decreases proliferation irrespective of metabolic activation system. CYN increases the frequency of necrotic cells in a dose- and time-dependent manner, whereas it has a very slight impact on apoptosis. Moreover, the presence of metabolic activation influences a susceptibility to necrotic cell death but not an apoptotic one. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0041-0101 1879-3150 |
DOI: | 10.1016/j.toxicon.2007.07.021 |